bluuebunny/crossref_metadata_2025 huggingface dataset:
A Benchmark Dose Analysis for Maternal Pregnancy Urine-Fluoride and IQ in Children
Authors: Grandjean Philippe , Hu Howard , Till Christine , Green Rivka , Bashash Morteza , Flora David , Tellez-Rojo Martha Maria , Song Peter , Lanphear Bruce , Budtz-Jørgensen Esben
Published: November 2020

As a safe exposure level for fluoride in pregnancy has not been established, we used data from two prospective studies for benchmark dose modeling. We included mother-child pairs from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort in Mexico and the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort in Canada. Children were assessed for IQ at age 4 (n=211) and between 6 and 12 years (n=287) in the ELEMENT cohort and between ages 3 and 4 years (n=512) in the MIREC cohort. We calculated covariate-adjusted regression coefficients and their standard errors to explore the concentration-effect function for maternal urinary fluoride with children’s IQ, including possible sex-dependence. Assuming a benchmark response of 1 IQ point, we derived benchmark concentrations (BMCs) of maternal urinary fluoride and benchmark concentration levels (BMCLs). No deviation from linearity was detected from the results of the two studies. Using a linear slope, the BMC for maternal urinary fluoride associated with a 1-point decrease in IQ scores of preschool-aged boys and girls was 0.29 mg/L (BMCL, 0.18 mg/L). The BMC was 0.30 mg/L (BMCL, 0.19 mg/L) when pooling the IQ scores from the older ELEMENT children and the MIREC cohort. Boys showed slightly lower BMC values compared with girls. Relying on two prospective studies, maternal urine-fluoride exposure at levels commonly occurring in the general population, the joint data showed BMCL results about 0.2 mg/L. These results can be used to guide decisions on preventing excess fluoride exposure in vulnerable populations.
What is the efficacy and safety of rapid exercise tests for exertional desaturation in Covid-19: A rapid review protocol
Authors: Kalin Asli , Javid Babak , Knight Matthew , Inada-Kim Matt , Greenhalgh Trisha
Published: November 2020

Background

Even when resting pulse oximetry is normal in the patient with acute Covid-19, hypoxia can manifest on exertion. We sought to summarise the literature on the performance of different rapid tests for exertional desaturation.

Research question

What tests have been formally evaluated for the rapid assessment of exertional hypoxia? What is the evidence for their accuracy, practicability and safety in the context of suspected acute Covid-19? To what extent will these tests help identify patients with evidence of either silent or hidden hypoxia leading to earlier recognition of those at risk of severe outcomes?

Method

We aim to review three independent searches of AMED, CINAHL, EMBASE MEDLINE, Cochrane and PubMed using LitCovid, Scholar and Google databases until 24thSeptember 2020. Screening, data abstraction, and quality appraisal of full-text papers will be completed independently by two reviewers including a topic expert and a review expert. Studies will be tabulated and assessed for risk of bias using QUADAS 2 tool.

Discussion

This rapid review aims to produce key findings relevant to the assessment of exertional desaturation in patients with suspected Covid-19. Establishing a validated tool to assess exertional desaturation will help to ensure that future research on this topic can be undertaken in a consistent way. An exertional desaturation test should be used in combination with a comprehensive clinical evaluation and only on patients whose resting oximetry reading is 96% or above unless in a supervised care setting. It should be terminated if the patient experiences adverse effects.
A publicly available score for evaluating hospital financial standing
Authors: Zinoviev Radoslav , Krumholz Harlan , Ciccarone Richard A. , Antle Rick , Forman Howard
Published: November 2020

A.

Objectives

To create a straightforward scoring procedure based on widely available, inexpensive financial data that provides an assessment of the financial health of a hospital.

Design

Methodological study.

Setting

Multicenter study.

Participants

All hospitals and health systems reporting the required financial metrics in 2017 were included for a total of 1,075 participants.

Interventions

We examined a list of 232 hospital financial indicators and used existing models and financial literature to select 30 metrics that sufficiently describe hospital operations. In a set of hospital financial data from 2017, we used Principal Coordinate Analysis to assess collinearity among variables and eliminated redundant variables. We isolated 10 unique variables, each assigned a weight equal to the share of its coefficient in a regression onto Moody’s Credit Rating, our predefined gold standard. The sum of weighted variables is a single composite score named the Yale Hospital Financial Score (YHFS).

Primary Outcome Measures

Ability to reproduce both financial trends from a “gold standard” metric and known associations with non-fiscal data.

Results

The validity of the YHFS was evaluated by: (1) assessing its reproducibility with previously excluded data; (2) comparing it to existing models; and, (3) replicating known associations with non-fiscal data. Ten percent of the initial dataset had been reserved for validation and was not used in creating the model; the YHFS predicts 96.7% of the variation in this reserved sample, demonstrating reproducibility. The YHFS predicts 90.5% and 88.8% of the variation in Moody’s and Standard and Poor’s bond ratings, respectively, supporting its validity. As expected, larger hospitals had higher YHFS scores whereas a greater share of Medicare discharges correlated with lower YHFS scores.

Conclusions

We created a reliable and publicly available composite score of hospital financial stability.

B.

Article Summary

Strengths and Limitations of This Study

There is a lack of models for assessing the financial state of hospitals in a robust and systematic way using publicly available data.

We created the Yale Hospital Financial Score, a compound financial ranking of hospitals using a diverse collection of hospital financial metrics.

The score ranks hospitals from 0 to 100 and was validated by showing reproducibility on a pre-excluded sample and strong correlation with “gold standard” metrics

This score has been developed to aid health policy researchers and has not yet been validated in studies of longitudinal financial outcomes
Cohorting of Non-Critically Ill COVID-19 Patients: A Multicenter Survey Study (COVID-COHORT)
Authors: Purohit Ushma , Fralick Mike
Published: November 2020

The COVID-19 pandemic has posed novel infection-control challenges for hospitals around the globe. One infection-control strategy that has been widely used in the context of other outbreaks is patient cohorting. This strategy refers to the placement of all patients exposed to the same laboratory-confirmed infectious agent in one location within the hospital. Little is known about the current utilization of this strategy with non-critically ill COVID-19 patients. An international multicenter, survey study was conducted to identify what strategies are planned or in place for patients with COVID-19 who are not critically ill. The survey was distributed from March 23-29th, 2020 to GIM physicians in Canada, USA, Denmark, Singapore, Hong Kong, and England. Of the 31 hospitals, 29 (94%) indicated that they plan on cohorting all GIM patients with COVID-19 to one location in the hospital. Among these 29 hospitals, 23 (79%) had implemented the plan at the time of the survey. The primary reasons for this decision were to limit the spread of COVID-19 and conserve PPE use. In conclusion, in the face of a novel virus there is near unanimity in the practice of patient cohorting as a potential mitigation strategy.
Encephalopathies associated with severe COVID-19 present specific neurovascular unit alterations without evidence of strong neuroinflammation
Authors: Bernard-Valnet Raphaël , Perriot Sylvain , Canales Mathieu , Pizzarotti Beatrice , Caranzano Leonardo , Castro-Jiménez Mayté , Epiney Jean-Benoit , Vijiala Sergiu , Chiabotti Paolo Salvioni , Anichini Angelica , Salerno Alexander , Jaton Katia , Vaucher Julien , Perreau Matthieu , Greub Gilbert , Pantaleo Giuseppe , Du Pasquier Renaud
Published: November 2020

Objective

Coronavirus disease (COVID-19) has been associated with a large variety of neurological disorders. However the mechanisms underlying these neurological complications remain elusive. In this study we aimed at determining whether neurological symptoms were caused by SARS-CoV-2 direct infection or by either systemic or local pro-inflammatory mediators.

Methods

We checked for SARS-CoV-2 RNA by RT-qPCR, SARS-CoV-2-specific antibodies and for 49 cytokines/chemokines/growth factors (by Luminex) in the cerebrospinal fluids (CSF) +/-sera of a cohort of 22 COVID-19 patients with neurological presentation and 55 neurological control patients (inflammatory [IND], non-inflammatory [NIND], multiple sclerosis [MS]).

Results

We detected SARS-CoV-2 RNA and virus-specific antibodies in the CSF of 0/22 and 10/21 COVID-19 patients, respectively. Of the four categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines and growth factors. In contrast, COVID-19 patients did not present overall upregulation of inflammatory mediators in the CSF. However, the CSF of patients with severe COVID-19 (ICU patients) exhibited higher concentrations of CCL2, CXCL8, and VEGF-A in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated barrier index and correlated to the increase of peripheral inflammation (serum HGF and CXCL10).

Conclusion

Our results point at an absence of massive SARS-CoV-2 infection or inflammation of the central nervous system, but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.
Rapid homogeneous assay for detecting antibodies against SARS-CoV-2
Authors: Rusanen Juuso , Kareinen Lauri , Levanov Lev , Mero Sointu , Pakkanen Sari H. , Kantele Anu , Amanat Fatima , Krammer Florian , Hedman Klaus , Vapalahti Olli , Hepojoki Jussi
Published: November 2020

Accurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and will help to examine possible vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (S) and nucleocapsid protein (N). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal generation.

We set up LFRET assays for antibodies against S and N and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described S construct and a novel N construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 S and N. We then compared the LFRET assays with these enzyme immunoassays and with a SARS-CoV-2 microneutralization test (MNT).

We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%).

In conclusion, this study demonstrates the applicability of LFRET, a 10-minute ‘mix and read’ assay, to detection of SARS-CoV-2 antibodies.
Precision shielding for COVID-19: metrics of assessment and feasibility of deployment
Authors: Ioannidis John P.A.
Published: November 2020

Background

The ability to preferentially protect high-groups in COVID-19 is hotly debated. Here, the aim is to present simple metrics of such precision shielding of people at high-risk of death after infection by SARS-CoV-2; demonstrate how they can estimated; and examine whether precision shielding was successfully achieved in the first COVID-19 wave.

Methods

The shielding ratio, S, is defined as the ratio of prevalence of infection among people at a high-risk group versus among people in a low-risk group. The contrasted risk groups examined here are according to age (>=70 versus <70 years), and institutionalized (nursing home) setting. For age-related precision shielding, data were used from large seroprevalence studies with separate prevalence data for elderly versus non-elderly and with at least 1000 assessed people >=70 years old. For setting-related precision shielding, data were analyzed from 10 countries where information was available on numbers of nursing home residents, proportion of nursing home residents among COVID-19 deaths, and overall population infection fatality rate.

Findings

Across 17 seroprevalence studies, the shielding ratio S for elderly versus non-elderly varied between 0.4 (substantial shielding) and 1.6 (substantial inverse protection, i.e. low-risk people being protected more than high-risk people). Five studies in USA all yielded S=0.4-0.8, consistent with some shielding being achieved, while two studies in China yielded S=1.5-1.6, consistent with inverse protection. Assuming 25% infection fatality rate among nursing home residents, S values for nursing home residents ranged from 0.07 to 3.1. The best shielding was seen in South Korea (S=0.07) and modest shielding was achieved in Israel, Slovenia, Germany, and Denmark. No shielding was achieved in Hungary and Sweden. In Belgium (S=1.9), UK (S=2.2) and Spain (S=3.1), nursing home residents were far more frequently infected that the rest of the population.

Interpretation

The experience from the first wave of COVID-19 suggests that different locations and settings varied markedly in the extent to which they protected high-risk groups. Both effective precision shielding and detrimental inverse protection can happen in real-life circumstances. COVID-19 interventions should seek to achieve maximal precision shielding.
Seroprevalence of SARS-CoV-2 antibodies in Saint Petersburg, Russia: a population-based study
Authors: Barchuk Anton , Skougarevskiy Dmitriy , Titaev Kirill , Shirokov Daniil , Raskina Yulia , Novkunkskaya Anastasia , Talantov Petr , Isaev Artur , Pomerantseva Ekaterina , Zhikrivetskaya Svetlana , Barabanova Lubov , Volkov Vadim
Published: November 2020

Background

Estimates from initial SARS-CoV-2 serological surveys were likely to be biased due to convenience sampling whereas large-scale population-based serosurveys could be biased due to non-response. This study aims to estimate the seroprevalence of SARS-CoV-2 infection in Saint Petersburg, Russia accounting for non-response bias.

Methods

We recruited a random sample of adults residing in St. Petersburg with random digit dialling. Computer-assisted telephone interview was followed by an invitation for an antibody test with randomized rewards for participation. Blood samples collected between May 27, 2020 and June 26, 2020 were assessed for anti-SARS-CoV-2 antibodies using two tests — CMIA and ELISA. The seroprevalence estimates were corrected for non-response bias, test sensitivity, and specificity. Individual characteristics associated with seropositivity were assessed.

Findings

66,250 individuals were contacted, 6,440 adults agreed to be interviewed and were invited to participate in the serosurvey. Blood samples were obtained from 1038 participants. Naïve seroprevalence corrected for test characteristics was 9.0% [95% CI 7.2–10.8] by CMIA and 10.8% [8.8–12.7] by ELISA. Correction for non-response bias decreased seroprevalence estimates to 7.4% [5.7–9.2] for CMIA and to 9.3% [7.4–11.2] for ELISA. The most pronounced decrease in non-response bias-corrected seroprevalence was attributed to the history of any illnesses in the past 3 months and COVID-19 testing. Besides that seroconversion was negatively associated with smoking status, self-reported history of allergies and changes in hand-washing habits.

Interpretation

These results suggest that even low estimates of seroprevalence in Europe’s fourth-largest city can be an overestimation in the presence of non-response bias. Serosurvey design should attempt to identify characteristics that are associated both with participation and seropositivity. Further population-based studies are required to explain the lower seroprevalence in smokers and participant reporting allergies.

Funding

Polymetal International plc
Advancing Human Genetics Research and Drug Discovery through Exome Sequencing of the UK Biobank
Authors: Szustakowski Joseph D. , Balasubramanian Suganthi , Sasson Ariella , Khalid Shareef , Bronson Paola G. , Kvikstad Erika , Wong Emily , Liu Daren , Davis J. Wade , Haefliger Carolina , Loomis A. Katrina , Mikkilineni Rajesh , Noh Hyun Ji , Wadhawan Samir , Bai Xiaodong , Hawes Alicia , Krasheninina Olga , Ulloa Ricardo , Lopez Alex , Smith Erin N. , Waring Jeff , Whelan Christopher D. , Tsai Ellen A. , Overton John , Salerno William , Jacob Howard , Szalma Sandor , Runz Heiko , Hinkle Greg , Nioi Paul , Petrovski Slavé , Miller Melissa R. , Baras Aris , Mitnaul Lyndon , Reid Jeffrey G.
Published: November 2020

The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a unique private/public partnership between the UK Biobank and eight biopharma companies that will sequence the exomes of all ∼500,000 UK Biobank participants. Here we describe early results from the exome sequence data generated by this consortium for the first ∼200,000 UKB subjects and the key features of this project that enabled the UKB-ESC to come together and generate this data.

Exome sequencing data from the first 200,643 UKB enrollees are now accessible to the research community. Approximately 10M variants were observed within the targeted regions, including: 8,086,176 SNPs, 370,958 indels and 1,596,984 multi-allelic variants. Of the ∼8M variants observed, 84.5% are coding variants and include 2,139,318 (25.3%) synonymous, 4,549,694 (53.8%) missense, 453,733 (5.4%) predicted loss-of-function (LOF) variants (initiation codon loss, premature stop codons, stop codon loss, splicing and frameshift variants) affecting at least one coding transcript. This open access data provides a rich resource of coding variants for rare variant genetic studies, and is particularly valuable for drug discovery efforts that utilize rare, functionally consequential variants.

Over the past decade, the biopharma industry has increasingly leveraged human genetics as part of their drug discovery and development strategies. This shift was motivated by technical advances that enabled cost-effective human genetics research at scale, the emergence of electronic health records and biobanks, and a maturing understanding of how human genetics can increase the probability of successful drug development. Recognizing the need for large-scale human genetics data to drive drug discovery, and the unique value of the open data access policies and contribution terms of the UK Biobank, the UKB-ESC was formed. This precompetitive collaboration has further strengthened the ties between academia and industry and provided teams an unprecedented opportunity to interact with and learn from the wider research community.
Ultra-rapid on-site detection of SARS-CoV-2 infection using simple ATR-FTIR spectroscopy and analysis algorithm: high sensitivity and specificity
Authors: Barauna Valério G. , Singh Maneesh N. , Barbosa Leonardo Leal , Marcarini Wena Dantas , Vassallo Paula Frizera , Mill Jose Geraldo , Ribeiro-Rodrigues Rodrigo , Warnke Patrick H. , Martin Francis L
Published: November 2020

There is an urgent need for ultra-rapid testing regimens to detect the SARS-CoV-2 [Severe Acute Respiratory Syndrome Coronavirus 2] virus infections in real-time within seconds to stop its spread. Current testing approaches for this RNA virus focus primarily on diagnosis by RT-qPCR, which is time-consuming, costly, often inaccurate and impractical for general population rollout due to the need for laboratory processing. The latency until the test result arrives with the patient has led to further virus spread. Furthermore, latest antigen rapid tests still require 15 to 30 min processing time and are challenging to handle. Despite increased PCR-test and antigen-test efforts the pandemic has entered the worldwide second stage. Herein, we applied a superfast reagent-free and non-destructive approach of attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy with subsequent chemometric analysis to the interrogation of virus-infected samples. Contrived samples with inactivated gamma-irradiated Covid-19 virus particles at levels down to 1582 copies/ml generated infrared (IR) spectra with good signal-to-noise ratio. Predominant virus spectral peaks are associated with nucleic acid bands, including RNA. At low copy numbers, the presence of virus particle was found to be capable of modifying the IR spectral signature of saliva, again with discriminating wavenumbers primarily associated with RNA. Discrimination was also achievable following ATR-FTIR spectral analysis of swabs immersed in saliva variously spiked with virus. Following on, we nested our test system in a clinical setting wherein participants were recruited to provide demographic details, symptoms, parallel RT-qPCR testing and the acquisition of pharyngeal swabs for ATR-FTIR spectral analysis. Initial categorisation of swab samples into negativeversuspositive Covid-19 infection was based on symptoms and PCR results. Following training and validation of a genetic algorithm-linear discriminant analysis (GA-LDA) algorithm, a blind sensitivity of 95% and specificity of 89% was achieved. This prompt approach generates results within two minutes and is applicable in areas with increased people traffic that require sudden test results such as airports, events or gate controls.
Caspases in COVID-19 Disease and Sequela and the Therapeutic Potential of Caspase Inhibitors
Authors: Plassmeyer Matthew , Alpan Oral , Corley Michael J. , Lillard Kimberleigh , Coatney Paige , Vaziri Tina , Michalsky Suzan , Premeaux Thomas A. , Pang Alina P.S. , Bukhari Zaheer , Yueng Stephen T. , Evering Teresa H , Naughton Gail , Latterich Martin , Mudd Philip , Spada Alfred , Rindone Nicole , Loizou Denise , Ndhlovu Lishomwa C. , Gupta Raavi
Published: November 2020

Currently, there is no effective vaccine and only one FDA approved early-stage therapy against SARS-CoV-2 infection as an indication to prevent disease progression. Cellular caspases play a role in the pathophysiology of a number of disorders that the co-morbid conditions seen in severe COVID-19 disease. In this study, we assessed transcriptional states of caspases in blood cells from COVID-19 patients. Gene expression levels of select caspases were increased inin vitroSARS-CoV-2 infection models and single cell RNA-Seq data of blood from COVID-19 patients showed a distinct caspase expression in T cells, neutrophils, and dendritic cells. Flow cytometric evaluation of CD4 T cells showed up-regulation of caspase-1 in hospitalized COVID-19 patients compared to unexposed controls. Convalescent COVID-19 patients with lingering symptoms (“long haulers”) showed persistent up-regulation of caspase-1 in CD4 T cells that was attenuatedex vivofollowing co-culture with a select pan-caspase inhibitor. Further, we observed elevated caspase-3 levels in red blood cells from COVID-19 patients compared to controls that were responsive to caspase inhibition. Our results expose an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19 outcomes.
Systematic review and meta-analysis of evidence on the efficacy of e-cigarette use for sustained smoking and nicotine cessation
Authors: Banks E , Yazidjoglou A , Brown S , Ford L , Zulfiqar T , Baenziger O , Joshy G.
Published: November 2020

Objective

To systematically review and meta-analyse evidence regarding the efficacy of electronic nicotine delivery systems (ENDS) as smoking cessation aids.

Data Sources

PubMed, Scopus, Web of Science, PsycINFO, MEDLINE and Cochrane Library were searched up to February-March 2020 (PROSPERO registration CRD42020170692).

Study selection

Published peer-reviewed randomised controlled trials (RCTs) of the efficacy of ENDS for sustained cessation of combustible tobacco smoking and/or nicotine use, compared with no intervention, placebo or nicotine replacement therapy (NRT) by intention-to-treat, with a minimum of four months follow-up.

Data Extraction

Data were extracted independently into a pre-specified template. Risk of bias was assessed with the Cochrane Collaboration’s tool and evidence quality rated using GRADE.

Data Synthesis

From 3,973 titles identified, nine RCTs were identified; 330 of 5,445 smokers randomised quit. Smoking cessation did notPublic health consequences differ significantly for randomisation to ENDS versus: no intervention (three studies, random-effects meta-analysis RR 1.95; 95%CI 0.90-4.22); placebo (three studies, 1.61; 0.93-2.78) or NRT (three studies; 1.25; 0.74-2.11). Fixed-effects sensitivity analyses showed significant results for ENDS vs NRT (1.43; 1.10-1.86). Smokers randomised to ENDS were substantially more likely than control to use nicotine at follow-up. Overall evidence quality was low. Considering only studies without potential competing interests further limited evidence but did not materially change conclusions.

Conclusions

There is insufficient evidence that ENDS are efficacious for smoking cessation compared to no intervention, placebo or NRT. Results are promising, particularly for therapeutic use, but vary according to analytic method. ENDS may lead to greater ongoing nicotine exposure than other smoking cessation methods.

Implications

This systematic review and meta-analysis consolidates current evidence on the efficacy of ENDS as an aid to sustained smoking and nicotine cessation and considers these findings in the context of potential competing interests. While findings are promising more research - preferably independent of industry funding - is needed to provide robust evidence of the efficacy of ENDS for smoking cessation. Future research should investigate nicotine cessation in addition to smoking cessation.
High attack rates of SARS-CoV-2 infection through household-transmission: a prospective study
Authors: Kuwelker Kanika , Zhou Fan , Blomberg Bjørn , Lartey Sarah , Brokstad Karl Albert , Trieu Mai Chi , Madsen Anders , Krammer Florian , Mohn Kristin GI , Tøndel Camilla , Linchausen Dagrunn Waag , Cox Rebecca J. , Langeland Nina , Bansal Amit , Corydon Annette , Real Francisco , Bredholt Geir , Bartsch Hauke , Sandnes Helene Heitmann , Vahokoski Juha , Jacobsen Kjerstin , Eidsheim Marianne , Sævik Marianne , Ertesvåg Nina Urke , Hauge Synnøve Ygre , Onyango Therese Bredholt
Published: November 2020

Background

Household attack rates of SARS-CoV-2 ranging from 7% to 38% have been reported, using reverse transcription polymerase chain reaction (RT-PCR) of respiratory samples. Lower attack rates were described in children, but the importance of age in household transmission dynamics remains to be clarified.

Methods

During the first month of the outbreak, we enrolled 112 households (291 participants) in a prospective case-ascertained study, collecting demographic and clinical data from index cases and household members. Sera were collected 6-8 weeks after index case symptom onset, to measure SARS-CoV-2-specific antibodies.

Findings

T Local Ethics Committee (#118664). he overall household attack rate was 45% assessed by seroconversion, and 47% when also including RT-PCR positives. Serology identified a significantly higher number of infected household members than RT-PCR. Attack rates were equally high in children (43%) and young adults (46%), but highest among household members aged ≥60 years (72%). The attack rate was 16% in asymptomatic household members, and 42% in RT-PCR negative household members. Older adults generally had higher antibody titres than younger adults. The risk of household transmission was higher when the index case had fever or dyspnoea during acute illness but not associated with cough.

Interpretation

Serological assays provide more accurate estimates of household secondary attack rate than RT-PCR, especially among children who have a lower RT-PCR positivity rate. Children are equally susceptible to infection as adults, but elderly show higher attack rates. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members.

Funding

Helse Vest (F-11628), Trond Mohn Foundation (TMS2020TMT05).
Are Mobile Phones part of the chain of transmission of SARS-CoV-2 in the hospital?
Authors: Sánchez Espinoza Evelyn Patricia , Farrel Marina Cortes , Nogueira Saidy Vasconez , de Paula Anderson Vicente , Guimarães Thais , Villas Boas Lucy Santos , Park Marcelo , da Silva Cristina Carvalho , Morales Ingra , Perdigão Neto Lauro Vieira , Tozetto-Mendoza Tania Regina , Boszczowski Icaro , Sabino Ester , Mendes-Correa Maria Cássia , Shafferman Levin Anna Sara , Costa Silvia Figueiredo
Published: November 2020

SARS-CoV-2 cross-transmission has become an concern in hospitals. We investigate healthcare workers(HCWs) knowledge about SARS-CoV-2 cross-transmission and conceptions whether the virus can remain on HCWs mobile phones(MPs) and be part of the chain of transmission.

A cross-sectional study was conducted at a COVID-19 Intensive Care Unit of a teaching-hospital. Fifty-one MPs were swabbed and a questionnaire about hand hygiene and MP use and disinfection was applied after an educational campaign. Although most of HCWs believed on the importance of cross-transmission and increased hand hygiene adhesion and MP disinfection during the pandemic, SARS-CoV-2 RNA was detected in two MPs(culture of the samples was negative).

Implementation of official hospital policies to guide HCWs regarding disinfection and care of personal MP are needed.
Effectiveness of quarantine and testing to prevent COVID-19 transmission from arriving travelers
Authors: Russell W. Alton , Buckeridge David L.
Published: November 2020

Objective

To assess the efficacy of policies designed to reduce the risk of international travelers importing SARS-CoV-2 into a country.

Method

We developed a simulation model and compared mandatory quarantine, testing, and combined quarantine and testing. We assessed the sensitivity of policy effectiveness to the timing of testing, compliance with quarantine and isolation, and other factors.

Results

In the base scenario, a 2-day quarantine reduced more risk than testing alone. The effectiveness of a 5-day quarantine requirement with perfect compliance was similar to a 14-day quarantine with moderate compliance. Testing 72h before arrival reduced less than 10% of in-country transmission risk across all scenarios. The addition of testing to quarantine added value for shorter quarantine lengths, when testing compliance was enforced, and when testing was performed near the end of quarantine.

Conclusions

Quarantine is more effective at preventing SARS-CoV-2 transmission from arriving travelers than testing alone, but testing combined with quarantine can add value if longer quarantine requirements are infeasible. Enforcing compliance with quarantine and isolation is critical. Requiring a negative test up to 72h before arrival may have limited effectiveness.
Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants: a prospective cohort study
Authors: Parker Edward P. K. , Bronowski Christina , Sindhu Kulandaipalayam Natarajan C. , Babji Sudhir , Benny Blossom , Carmona-Vicente Noelia , Chasweka Nedson , Chinyama End , Cunliffe Nigel A. , Dube Queen , Giri Sidhartha , Grassly Nicholas C. , Gunasekaran Annai , Howarth Deborah , Immanuel Sushil , Jere Khuzwayo C. , Kampmann Beate , Lowe Jenna , Mandolo Jonathan , Praharaj Ira , Rani Bakthavatsalam Sandya , Silas Sophia , Srinivasan Vivek Kumar , Turner Mark , Venugopal Srinivasan , Verghese Valsan Philip , Darby Alistair C. , Kang Gagandeep , Iturriza-Gómara Miren
Published: November 2020

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. We measured maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. ORV shedding and seroconversion rates were significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk were negatively correlated with ORV response in India and Malawi, and this was mediated partly by a reduction in ORV replication. In the UK, ORV replication was not inhibited despite comparable maternal antibody levels. In both India and Malawi, pre-vaccination microbiota diversity was negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.
HIV TREATMENT OUTCOMES IN RURAL GEORGIA USING TELEMEDICINE
Authors: Lawal Folake J. , Omotayo Moshood O. , Lee Tae Jin , Rao Arni S.R. Srinivasan , Vazquez Jose A.
Published: November 2020

Background

The dearth of specialized healthcare services contributes to the ongoing HIV epidemic. Telemedicine (TM) is a potential tool to improve HIV care, but little is known about its effectiveness when compared to traditional (face-to-face) (F2F) care in rural populations. The objective of this study is to examine the effectiveness of HIV care delivered through TM compared to F2F care.

Methods

We conducted a retrospective chart review of a subset of HIV patients who attended TM clinic in Dublin Georgia, and conventional F2F clinic in Augusta, Georgia between May 2017 to April 2018. All TM patients were matched to F2F patients based on gender, age, and race. HIV Viral Load (VL) and gain in CD4 counts were compared using T-test and Snedecor Statistics.

Results

385 patients were included in the analyses (F2F=200, TM=185). Mean CD4 in the TM group was higher (643.9 cells/mm3) than the F2F group (596.3 cells/mm3) (p< 0.001). There was no statistically significant difference in VL reduction and control. Thirty-eight of eighty-five patients with detectable VL achieved viral suppression during the study period (F2F = 24/54, TM =14/31), with a mean change of −3.34 × 104and −1.24 × 104respectively, p = 1.00. Mean VL was F2F = 416.8 cp/ml, TM = 713.4 cp/ml, p = 0.3.

Conclusion

TM was associated with outcome measures comparable to F2F. Increased access to specialty HIV care through TM can facilitate HIV control in communities with limited healthcare access in rural US. Rigorous prospective evaluation of TM for HIV care effectiveness is warranted.

Article Summary

Telemedicine can be useful in improving access to specialist outpatient care for HIV and other chronic diseases, in remote communities with limited resources. Telemedicine can lead to similar outcomes when compared to traditional face-to-face outpatient consultations. This is especially true currently with COVID-19.
Profiling SARS-CoV-2 mutation fingerprints that range from the viral pangenome to individual infection quasispecies
Authors: Lau Billy T. , Pavlichin Dmitri , Hooker Anna C. , Almeda Alison , Shin Giwon , Chen Jiamin , Sahoo Malaya K. , Huang ChunHong , Pinsky Benjamin A. , Lee HoJoon , Ji Hanlee P.
Published: November 2020

Background

The genome of SARS-CoV-2 is susceptible to mutations during viral replication due to the errors generated by RNA-dependent RNA polymerases. These mutations enable the SARS-CoV-2 to evolve into new strains. Viral quasispecies emerge from de novo mutations that occur in individual patients. In combination, these sets of viral mutations provide distinct genetic fingerprints that reveal the patterns of transmission and have utility in contract tracing.

Methods

Leveraging thousands of sequenced SARS-CoV-2 genomes, we performed a viral pangenome analysis to identify conserved genomic sequences. We used a rapid and highly efficient computational approach that relies on k-mers, short tracts of sequence, instead of conventional sequence alignment. Using this method, we annotated viral mutation signatures that were associated with specific strains. Based on these highly conserved viral sequences, we developed a rapid and highly scalable targeted sequencing assay to identify mutations, detect quasispecies and identify mutation signatures from patients. These results were compared to the pangenome genetic fingerprints.

Results

We built a k-mer index for thousands of SARS-CoV-2 genomes and identified conserved genomics regions and landscape of mutations across thousands of virus genomes. We delineated mutation profiles spanning common genetic fingerprints (the combination of mutations in a viral assembly) and rare ones that occur in only small fraction of patients. We developed a targeted sequencing assay by selecting primers from the conserved viral genome regions to flank frequent mutations. Using a cohort of SARS-CoV-2 clinical samples, we identified genetic fingerprints consisting of strain-specific mutations seen across populations and de novo quasispecies mutations localized to individual infections. We compared the mutation profiles of viral samples undergoing analysis with the features of the pangenome.

Conclusions

We conducted an analysis for viral mutation profiles that provide the basis of genetic fingerprints. Our study linked pangenome analysis with targeted deep sequenced SARS-CoV-2 clinical samples. We identified quasispecies mutations occurring within individual patients, mutations demarcating dominant species and the prevalence of mutation signatures, of which a significant number were relatively unique. Analysis of these genetic fingerprints may provide a way of conducting molecular contact tracing.
Preferential observation of large infectious disease outbreaks leads to consistent overestimation of intervention efficacy
Authors: Zelner Jon , Masters Nina , Broen Kelly , Lofgren Eric
Published: November 2020

Data from infectious disease outbreaks in congregate settings are often used to elicit clues about which types of interventions may be useful in other facilities. This is commonly done using before-and-after comparisons in which the infectiousness of pre-intervention cases is compared to that of post-intervention cases and the difference is attributed to intervention impact. In this manuscript, we show how a tendency to preferentially observe large outbreaks can lead to consistent overconfidence in how effective these interventions actually are. We show, in particular, that these inferences are highly susceptible to bias when the pathogen under consideration exhibits moderate-to-high amounts of heterogeneity in infectiousness. This includes important pathogens such as SARS-CoV-2, influenza, Noroviruses, HIV, Tuberculosis, and many others
Mantis: flexible and consensus-driven genome annotation
Authors: Queirós Pedro , Delogu Francesco , Hickl Oskar , May Patrick , Wilmes Paul
Published: November 2020

Background

The past decades have seen a rapid development of the (meta-)omics fields, producing an unprecedented amount of data. Through the use of well-characterized datasets we can infer the role of previously functionally unannotated proteins from single organisms and consortia. In this context, protein function annotation allows the identification of regions of interest (i.e. domains) in protein sequences and the assignment of biological functions. Despite the existence of numerous tools, some challenges remain, specifically in terms of speed, flexibility, and reproducibility. In the era of big data it also becomes increasingly important to cease limiting our findings to a single reference, coalescing knowledge from different data sources, thus overcoming some limitations in overly relying on computationally generated data.

Results

We implemented a protein annotation tool - Mantis, which uses text mining to integrate knowledge from multiple reference data sources into a single consensus-driven output. Mantis is flexible, allowing for total customization of the reference data used, adaptable, and reproducible across different research goals and user environments. We implemented a depth-first search algorithm for domain-specific annotation, which led to an average 0.038 increase in precision when compared to sequence-wide annotation. Mantis is fast, annotating an average genome in 25-40 minutes, whilst also outputting high-quality annotations (average coverage 81.4%, average precision 0.892).

Conclusions

Mantis is a protein function annotation tool that produces high-quality consensusdriven protein annotations. It is easy to set up, customize, and use, scaling from single genomes to large metagenomes. Mantis is available under the MIT license available athttps://github.com/PedroMTQ/mantis.
Navigating through chemical space and evolutionary time across the Australian continent in plant genusEremophila
Authors: Gericke Oliver , Fowler Rachael M. , Heskes Allison M. , Bayly Michael J. , Semple Susan J. , Ndi Chi P. , Stærk Dan , Løland Claus J. , Murphy Daniel J. , Buirchell Bevan J. , Møller Birger L.
Published: November 2020

Eremophilais the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize manyEremophilaspecies as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships betweenEremophilaand related genera in the tribe. Unique and structurally diverse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite diversity in a chemo-evolutionary framework applying a combination of molecular phylogenetic and state-of-the-art computational metabolomics tools to build a dataset involving leaf samples from a total of 291 specimens ofEremophilaand allied genera. The chemo-evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution) and medicinal properties (traditional medicinal uses and antibacterial studies) augmenting our understanding of complex interactions in biological systems.
Runcer-Necromancer: A Method To Rescue Data From An Interrupted Run On MGISEQ-2000
Authors: Pavlova Anna , Belova Vera , Afasizhev Robert , Bulusheva Irina , Rebrikov Denis , Korostin Dmitriy
Published: November 2020

During the sequencing process, problems can occur with any device including the MGISEQ-2000 (DNBSEQ-G400) platform. We encountered a power outage that resulted in a temporary shutdown of a sequencer in the middle of the run. Since barcode reading in MGISEQ-2000 takes place at the end of the run, it was impossible to use non-demultiplexed raw data. We decided to completely use up the same cartridge with reagents and flow cell loaded with DNB and started a new run in a shortened custom mode. We figured out how the MGISEQ-2000 converts preliminary data in .cal format into .fastq files and wrote a script named “Runcer-Necromacer” for merging .fastq files based on the analysis of their headers (available online:https://github.com/genomecenter/runcer-necromancer). Read merging proved to be possible because the MGISEQ-2000 flow cell has a patterned structure and each DNB has invariable coordinates on it, regardless of its position on the flow cell stage. We demonstrated the correctness of data merging by comparing sample analysis results with previously obtained .fastq files for them. Thus, we confirmed that it is possible to restart the device and save both parts of the interrupted run.
Testing alternative phylogenetic hypotheses for the tent tortoise species complex (Reptilia, Testudinidae) using multiple data types and methods
Authors: Zhao Zhongning , Heideman Neil , Oosthuizen Jaco , Hofmeyr Margaretha D.
Published: November 2020

We examined genetic differentiation in the highly polymorphic and taxonomically confusing tent tortoise (Psammobates tentorius) species complex in southern Africa, using three types of molecular markers (nDNA, mtDNA and microsatellite DNA) and morphological data. The Approximate Bayesian Computation based simulation analyses advocated an alternative phylogenetic hypothesis for the tent tortoise species complex, which was better and more inclusive in explaining its genealogical history. Based on the evidence derived from the sequence, microsatellite and morphology data, a four species scheme (among the seven mtDNA clades) appears to be the best taxonomic solution for the systematic puzzle of theP. tentoriusspecies complex, namely, “C1+C4+C5+C7”, “C3”, “C2” and “C6”. The microsatellite datasets yielded similar genetic structure and gene flow patterns among the seven mtDNA clades in comparison to the sequence DNA. Evidence was found of possible hybridization between C1 and C2 in their intergradation zone, but not between C2 and C4. Results of the inbreeding analyses provided strong evidence of inbreeding in the eastern population of C1 and southern population of C2, which may be indicative of a bottleneck effect.
Learning to live with Dale’s principle: ANNs with separate excitatory and inhibitory units
Authors: Cornford Jonathan , Kalajdzievski Damjan , Leite Marco , Lamarquette Amélie , Kullmann Dimitri M. , Richards Blake
Published: November 2020

Abstract

The units in artificial neural networks (ANNs) can be thought of as abstractions of biological neurons, and ANNs are increasingly used in neuroscience research. However, there are many important differences between ANN units and real neurons. One of the most notable is the absence of Dale’s principle, which ensures that biological neurons are either exclusively excitatory or inhibitory. Dale’s principle is typically left out of ANNs because its inclusion impairs learning. This is problematic, because one of the great advantages of ANNs for neuroscience research is their ability to learn complicated, realistic tasks. Here, by taking inspiration from feedforward inhibitory interneurons in the brain we show that we can develop ANNs with separate populations of excitatory and inhibitory units that learn just as well as standard ANNs. We call these networks Dale’s ANNs (DANNs). We present two insights that enable DANNs to learn well: (1) DANNs are related to normalization schemes, and can be initialized such that the inhibition centres and standardizes the excitatory activity, (2) updates to inhibitory neuron parameters should be scaled using corrections based on the Fisher Information matrix. These results demonstrate how ANNs that respect Dale’s principle can be built without sacrificing learning performance, which is important for future work using ANNs as models of the brain. The results may also have interesting implications for how inhibitory plasticity in the real brain operates.