bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy management strategy for super capacitor energy storage system based on phase shifted full bridge converter
Authors: Lin Baode
Published: April 2021

In order to improve the efficiency and extend the service life of supercapacitors, this paper proposes a supercapacitor energy management method based on phase-shifted full-bridge converter. The method uses the supercapacitor state of charge (SOC) as a reference and combines the DC bus voltage fluctuation to quickly control the energy bidirectional flow. The simulation is carried out in Matlab/Simulink. The simulation results show that the proposed method combines SOC estimation and energy conversion, which can realize the optimal management of super capacitor and has fast dynamic response capability.
An evergreen mind and a heart for the colors of fall
Authors: Aubry Sylvain , Christ Bastien , Kräutler Bernhard , Martinoia Enrico , Thomas Howard , Zipfel Cyril
Published: April 2021

With the finest biochemical and molecular approaches, convincing explorative strategies, and long-term vision, Stefan Hörtensteiner succeeded in elucidating the biochemical pathway responsible for chlorophyll degradation. After having contributed to the identification of key chlorophyll degradation products in the course of the past 25 years, he gradually identified and characterized most of the crucial players in the PAO/phyllobilin degradation pathway of chlorophyll. He was one of the brightest plant biochemists of his generation, and his work opened doors to a better understanding of plant senescence, tetrapyrrole homeostasis, and their complex regulation. He sadly passed away on 5 December 2020, aged 57.
Telerehabilitation During the COVID-19 Pandemic in Outpatient Rehabilitation Settings: A Descriptive Study
Authors: Werneke Mark W , Deutscher Daniel , Grigsby David , Tucker Carole A , Mioduski Jerome E , Hayes Deanna
Published: April 2021

Objective

COVID-19 has widely affected delivery of health care. In response, telerehabilitation (TR) has emerged as alternative care model. Aims were: (1) to describe baseline patient characteristics and available unadjusted outcomes for episodes of care administered during COVID-19 using TR versus traditional in-person care, and (2) to describe TR frequency levels by condition and telecommunication modes.

Methods

A descriptive retrospective observational design was used to report patient variables and outcomes including physical function, number of visits, and patient satisfaction, by TR frequency (few, most, or all visits) and telecommunication modes. Standardized differences were used to compare baseline characteristics between episodes with and without TR.

Results

Sample consisted of 222,680 patients (59% female; mean [SD] age = 55 [18] years). Overall TR rate was 6% decreasing from 10% to 5% between second and third quarters of 2020. Outcome measures were available for 90% to 100% of episodes. Thirty-seven percent of clinicians administered care via TR. Patients treated using TR compared with in-person care were more likely to be younger and live in large metropolitan areas. From those with TR, 55%, 20%, and 25% had TR during few, most, or all visits, respectively. TR care was administered equally across orthopedic body parts, with lower use for nonorthopedic conditions such as stroke, edema, and vestibular dysfunction. TR was primarily administered using synchronous (video or audio) modes. The rate of patients reported being very satisfied with their treatment results was 3% higher for no TR compared with TR.

Conclusions

These results provide new knowledge about to whom and how TR is being administered during the pandemic in outpatient rehabilitation practices throughout the United States. The database assessed was found to be suitable for conducting studies on associations between TR and diverse outcome measures, controlling for a comprehensive set of patient characteristics, to advance best TR care models, and promote high-quality care.

Impact

This study provided detailed and robust descriptive information using an existing national patient database containing patient health and demographic characteristics, outcome measures, and telerehabilitation (TR) administration data. Findings support the feasibility to conduct future studies on associations between TR care and patient outcomes, adjusting for a wide range of patient characteristics and clinical setting factors that may be associated with the probability of receiving TR. The finding of limited and decreasing use of TR over the study period calls for studies aimed to better understand facilitators and inhibitors of TR use by rehabilitation therapists during everyday practice to promote its use when clinically appropriate.
Species Tree Estimation from Gene Trees by Minimizing Deep Coalescence and Maximizing Quartet Consistency: A Comparative Study and the Presence of Pseudo Species Tree Terraces
Authors: Farah Ishrat Tanzila , Islam Muktadirul , Zinat Kazi Tasnim , Rahman Atif Hasan , Bayzid Shamsuzzoha
Published: April 2021

Species tree estimation from multilocus data sets is extremely challenging, especially in the presence of gene tree heterogeneity across the genome due to incomplete lineage sorting (ILS). Summary methods have been developed which estimate gene trees and then combine the gene trees to estimate a species tree by optimizing various optimization scores. In this study, we have extended and adapted the concept of phylogenetic terraces to species tree estimation by “summarizing” a set of gene trees, where multiple species trees with distinct topologies may have exactly the same optimality score (i.e., quartet score, extra lineage score, etc.). We particularly investigated the presence and impacts of equally optimal trees in species tree estimation from multilocus data using summary methods by taking ILS into account. We analyzed two of the most popular ILS-aware optimization criteria: maximize quartet consistency (MQC) and minimize deep coalescence (MDC). Methods based on MQC are provably statistically consistent, whereas MDC is not a consistent criterion for species tree estimation. We present a comprehensive comparative study of these two optimality criteria. Our experiments, on a collection of data sets simulated under ILS, indicate that MDC may result in competitive or identical quartet consistency score as MQC, but could be significantly worse than MQC in terms of tree accuracy—demonstrating the presence and impacts of equally optimal species trees. This is the first known study that provides the conditions for the data sets to have equally optimal trees in the context of phylogenomic inference using summary methods. [Gene tree; incomplete lineage sorting; phylogenomic analysis, species tree; summary method.]
Promotion effects of DEHP on hepatocellular carcinoma models: up-regulation of PD-L1 by activating the JAK2/STAT3 pathway
Authors: Xu Qiang , Huang Song , Xu Zi-Ming , Ji Ke , Zhang Xiang , Xu Wei-Ping , Wei Wei
Published: April 2021

Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.
Convalescent Plasma Use in the United States was inversely correlated with COVID-19 Mortality: Did Plasma Hesitancy cost lives?
Authors: Casadevall Arturo , Dragotakes Quigly , Johnson Patrick W. , Senefeld Jonathon W. , Klassen Steven A. , Wright R. Scott , Joyner Michael J , Paneth Nigel , Carter Rickey E.
Published: April 2021

Background

The US Food and Drug Administration authorized Convalescent Plasma (CCP) therapy for hospitalized COVID-19 patients via the Expanded Access Program (EAP) and the Emergency Use Authorization (EUA), leading to use in about 500,000 patients during the first year of the pandemic for the US.

Methods

We tracked the number of CCP units dispensed to hospitals by blood banking organizations and correlated that usage with hospital admission and mortality data.

Results

CCP usage per admission peaked in Fall 2020, with more than 40% of inpatients estimated to have received CCP between late September and early November 2020. However, after randomized controlled trials failed to show a reduction in mortality, CCP usage per admission declined steadily to a nadir of less than 10% in March 2021. We found a strong inverse correlation (r = −0.52, P = 0.002) between CCP usage per hospital admission and deaths occurring two weeks after admission, and this finding was robust to examination of deaths taking place one, two or three weeks after admission. Changes in the number of hospital admissions, SARS-CoV-2 variants, and age of patients could not explain these findings. The retreat from CCP usage might have resulted in as many as 29,000 excess deaths from mid-November 2020 to February 2021.

Conclusions

A strong inverse correlation between CCP use and mortality per admission in the USA provides population level evidence consistent with the notion that CCP reduces mortality in COVID-19 and suggests that the recent decline in usage could have resulted in excess deaths.
Optimal policy determination in sequential systemic and locoregional therapy of oropharyngeal squamous carcinomas: A patient-physician digital twin dyad with deep Q-learning for treatment selection
Authors: Tardini Elisa , Zhang Xinhua , Canahuate Guadalupe , Wentzel Andrew , Mohamed Abdallah S. R. , Van Dijk Lisanne , Fuller Clifton D. , Marai G. Elisabeta
Published: April 2021

Purpose

Currently, selection of patients for sequential vs. concurrent chemotherapy/radiation regimens lacks evidentiary support, and it is based on locally-optimal decisions for each step. We aim to optimize the multi-step treatment of head and neck cancer patients and to predict multiple patient survival and toxicity outcomes, and we develop, apply, and evaluate a first application of deep-Q-learning (DQL) and simulation to this problem.

Patients and methods

The treatment decision DQL digital twin and the patient’s digital twin were created, trained and evaluated on a dataset of 536 oropharyngeal squamous cell carcinoma (OPC) patients with the goal of, respectively, determining the optimal treatment decisions with respect to survival and toxicity metrics, and predicting the outcomes of the optimal treatment on the patient. The models were trained on a subset of 402 patients (split randomly) and evaluated on a separate set of 134 patients. Training and evaluation of the digital twin dyad was completed in August 2020. The dataset includes 3-step sequential treatment decisions and complete relevant history of the patients cohort treated at MD Anderson Cancer Center between 2005 and 2013, with radiomics analysis performed for the segmented primary tumor volumes.

Results

On the validation set, 87.09% mean and 90.85% median accuracy in treatment outcome prediction, matching the clinicians’ outcomes and improving (predicted) survival rate by +3.73% (95% CI: [-0.75%, +8.96%]), and dysphagia rate by +0.75% (CI: [-4.48%, +6.72%]) when following DQL treatment decisions.

Conclusion

Given the prediction accuracy and predicted improvement on medically relevant outcomes yielded by this approach, this digital twin dyad of the patient-physician dynamic treatment problem has the potential of aiding physicians in determining the optimal course of treatment and in assessing its outcomes.
Outward and inward protections of different mask designs for different respiratory activities
Authors: Koh Xue Qi , Sng Anqi , Chee Jing Yee , Sadovoy Anton , Luo Ping , Daniel Dan
Published: April 2021

We evaluate the outward and inward protections of different mask types (N95, surgical and two cloth mask designs) taking into account the imperfect fit on the wearer. To this end, we built a manikin to simulate exhaling, coughing and inhaling of aerosol droplets 0.3–5.0 µm in diameters. The outward and inward protections depend on many factors, including the droplet size, the mask fit and the presence of a filter layer. Here, we show that cloth and surgical masks with a non-woven filter layer can achieve a combined outward and inward protections between 50% and 90%. Removing the filter layer greatly reduces the protection efficiency to below 20% for the smallest droplet size. While a well-fitted N95 masks offer protection efficiency close to 100%, a poorly fitted N95 mask with gaps offers less protection than a well-fitted surgical/cloth mask. We also found that double masking—the wearing of cloth mask on top of a surgical mask—is only effective at reducing outward droplet emissions when coughing, while offering no additional protection when exhaling/inhaling as compared to a single cloth/surgical mask. The results of our work can inform the implementation of mask mandates to minimize airborne transmissions of coronavirus disease of 2019 (COVID-19).

Practical implications

A single cloth/surgical mask with non-woven filter layer offers significant protection against airborne transmissions.

Filtering facepiece masks such as N95 respirators are unlikely to achieve the advertised high protection for the general public due to poor mask fit.

Double-masking offers little to no additional protection over a single cloth/surgical mask.
Invasive airway “Intubation” in COVID-19 patients :statistics, causes and recommendations
Authors: Mohammadi Mostafa , Pour Khamseh Alireza Khafaee , Varpaei Hesam Aldin
Published: April 2021

Background

Severe COVID-19 disease could induce acute respiratory distress which is characterized by tachypnea, hypoxia, and dyspnea. Intubation and mechanical ventilation are a strategic treatment of COVID-19 distress or hypoxia.

Methods

We searched PubMed, Embase, and Scopus databases through April 1, 2021, to identify relevant randomized control trials, observational studies, and case series.

Results

24 studies were included in this review. Studies were conducted in the USA, China, Spain, South Korea, Italy, Iran, and Brazil. Most patients were intubated in the intensive care unit. Rapid sequence induction was mostly used for intubation. ROX index might be utilized for the predictor of the necessity of intubation in COVID-19 patients. According to the previous studies the rate of intubation reported 5 to 88%. It was revealed that 1.4 - 44.5% of patients might be extubated. Yet obesity and age (elderly) are the only risk factors of delayed or difficult extubation.

Discussion and conclusion

Acute respiratory distress in COVID-19 patients could require endotracheal intubation and mechanical ventilation. Severe respiratory distress, loss of consciousness, and hypoxia were the most important reasons for intubation. Also, increased levels of ferritin, d-dimer, and lipase in common with hypoxia are correlated with intubation and ICU admission Mortality following intubation is reported to be 15 to 36%. Awake-prone positioning in comparison to high-flow nasal oxygen therapy did not reduce the risk of intubation and mechanical ventilation. There was no association between intubation timing and mortality of infected patients. noninvasive ventilation may have survival benefits.
North West London Covid-19 Vaccination Programme: Real-world evidence for Vaccine uptake and effectiveness
Authors: Glampson B , Brittain J , Kaura Amit , Mulla A , Mercuri L , Brett S , Aylin P , Sandall T , Goodman I , Redhead J , Saravanakumar K , Mayer E K
Published: April 2021

Objective

To assess the early vaccine administration coverage and vaccine effectiveness and outcome data across an integrated care system of eight CCGs leveraging a unique population-level care dataset

Design

Retrospective cohort study.

Setting

Individuals eligible for COVID 19 vaccination in North West London based on linked primary and secondary care data.

Participants

2,183,939 individuals eligible for COVID 19 vaccination

Results

During the NWL vaccine programme study time period 5.88% of individuals declined and did not receive a vaccination. Black or black British individuals had the highest rate of declining a vaccine at 16.14% (4,337). There was a strong negative association between deprivation and rate of declining vaccination (r=-0.94, p<0.01) with 13.5% of individuals declining vaccination in the most deprived postcodes compared to 0.98% in the least deprived postcodes.

In the first six days after vaccination 344 of 389587 individuals tested positive for COVID-19 (0.09%). The rate increased to 0.13% (525/389,243) between days 7 and 13, before then gradually falling week on week.

At 28 days post vaccination there was a 74% (HR 0.26 (0.19-0.35)) and 78% (HR 0.22 (0.18-0.27)) reduction in risk of testing positive for COVID-19 for individuals that received the Oxford/Astrazeneca and Pfizer/BioNTech vaccines respectively, when compared with unvaccinated individuals.

After vaccination very low rates of hospital admission were seen in individuals testing positive for COVID-19 (0.01% of all patients vaccinated).

Conclusions

This study provides further evidence that a single dose of either the Pfizer/BioNTech vaccine or the Oxford/Astrazeneca vaccine is effective at reducing the risk of testing positive for COVID-19 up to 60 days across all adult age groups, ethnic groups, and risk categories in an urban UK population. There was no difference in effectiveness up to 28 days between the Oxford/Astrazeneca and Pfizer/BioNtech vaccines.

In those declining vaccination higher rates were seen in those living in the most deprived areas and in Black and Black British groups.

There was no definitive evidence to suggest COVID-19 was transmitted as a result of vaccination hubs during vaccine the administration roll-out in NWL, and the risk of contracting COVID-19 and/or becoming hospitalised after vaccination has been demonstrated to be very low in the vaccinated population.
Emergence of multiple SARS-CoV-2 antibody escape variants in an immunocompromised host undergoing convalescent plasma treatment
Authors: Chen Liang , Zody Michael C , Mediavilla Jose R , Cunningham Marcus H , Composto Kaelea , Chow Kar Fai , Kordalewska Milena , Corvelo André , Oschwald Dayna M , Fennessey Samantha , Zetkulic Marygrace , Dar Sophia , Kramer Yael , Mathema Barun , Maniatis Tom , Perlin David S , Kreiswirth Barry N
Published: April 2021

SARS-CoV-2 Variants of Concerns (VOC), e.g., B.1.351 (20H/501Y.V2) and P1 (20J/501Y.V3), harboring N-terminal domain (NTD) or the receptor-binding domain (RBD) (e.g., E484K) mutations, exhibit reduced in vitro susceptibility to convalescent serum, commercial antibody cocktails, and vaccine neutralization, and have been associated with reinfection. The accumulation of these mutations could be the consequence of intra-host viral evolution due to prolonged infection in immunocompromised hosts. In this study, we document the microevolution of SARS-CoV-2 recovered from sequential tracheal aspirates from an immunosuppressed patient on tacrolimus, steroids and convalescent plasma therapy, and identify the emergence of multiple NTD and RBD mutations associated with reduced antibody neutralization as early as three weeks after infection. SARS-CoV-2 genomes from the first swab (Day 0) and three tracheal aspirates (Day 7, 21 and 27) were compared at the sequence level. We identified five different S protein mutations at the NTD or RBD regions from the second tracheal aspirate sample (21 Day). The S:Q493R substitution and S:243-244LA deletion had ∼70% frequency, while ORF1a:A138T, S:141-144LGVY deletion, S:E484K and S:Q493K substitutions demonstrated ∼30%, ∼30%, ∼20% and ∼10% mutation frequency, respectively. However, the third tracheal aspirate sample collected one week later (Day 27) was predominated by the haplotype of ORF1a:A138T, S:141-144LGVY deletion and S:E484K (> 95% mutation frequency). Notably, S protein deletions (141-144LGVY and 243-244LA deletions in NTD region) and substitutions (Q493K/R and E484K in the RBD region) previously showed reduced susceptibly to monoclonal antibody or convalescent plasma. The observation supports the hypothesis that VOCs can independently arise and that immunocompromised patients on convalescent plasma therapy are potential breeding grounds for immune-escape mutants.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The study was in part supported by Center for Discovery and Innovation and Hackensack Meridian Health Foundation.
Development of a tool to prioritize the monitoring of COVID-19 patients by public health teams
Authors: Vecino-Ortiz Andres I. , Guzman-Tordecilla Nicolás , Ruiz Yenny Fernanda Guzmán , Peñaloza-Quintero Rolando Enrique , Fernández-Niño Julián A. , Gomez Fernando Ruiz , Trujillo Antonio J.
Published: April 2021

Background

In the context of the COVID-19 pandemic, public health teams have struggled to conduct monitoring for confirmed or suspicious COVID-19 patients. However, monitoring these patients is critical to improving the chances of survival, and therefore, a prioritization strategy for these patients is warranted. This study developed a monitoring algorithm for COVID-19 patients for the Colombian Ministry of Health and Social Protection (MOH).

Methods

This work included 1) a literature review, 2) consultations with MOH and National Institute of Health officials, and 3) data analysis of all positive COVID-19 cases and their outcomes. We used clinical and socioeconomic variables to develop a set of risk categories to identify severe cases of COVID-19.

Results

This tool provided four different risk categories for COVID-19 patients. As soon as the time of diagnosis, this tool can identify 91% of all severe and fatal COVID-19 cases within the first two risk categories.

Conclusion

This tool is a low-cost strategy to prioritize patients at higher risk of experiencing severe COVID-19. This tool was developed so public health teams can focus their scarce monitoring resources on individuals at higher mortality risk. This tool can be easily adapted to the context of other lower and middle-income countries. Policymakers would benefit from this low-cost strategy to reduce COVID-19 mortality, particularly during outbreaks.
DNA methylation and brain dysmaturation in preterm infants
Authors: Wheater Emily N. W. , Galdi Paola , McCartney Daniel L. , Blesa Manuel , Sullivan Gemma , Stoye David Q. , Lamb Gillian , Sparrow Sarah , Murphy Lee , Wrobel Nicola , Quigley Alan J. , Semple Scott , Thrippleton Michael J. , Wardlaw Joanna M. , Bastin Mark E. , Marioni Riccardo E. , Cox Simon R. , Boardman James P.
Published: April 2021

Preterm birth is associated with dysconnectivity of structural brain networks and is a leading cause of neurocognitive impairment in childhood. Variation in DNA methylation (DNAm) is associated with early exposure to extrauterine life but there has been little research exploring its relationship with brain development.

Using genome-wide DNA methylation data from saliva of 258 neonates, we investigated the impact of gestational age on the methylome and performed functional analysis to identify enriched gene sets from probes that contributed to differentially methylated probes (DMPs) or regions (DMRs). We tested the hypothesis that variation in DNAm could underpin the association between preterm birth and atypical brain development by linking DMPs with measures of white matter connectivity derived from diffusion MRI metrics: peak width of skeletonised mean diffusivity (PSMD), fractional anisotropy (PSFA) and neurite density index (PSNDI).

Gestational age at birth was associated with widespread differential methylation, with genome-wide significant associations observed for 8,870 CpG probes (p<3.6×10−8) and 1,767 differentially methylated regions. Functional analysis identified 14 enriched gene ontology terms pertaining to cell-cell contacts and cell-extracellular matrix contacts. Principal component analysis of probes with genome-wide significance revealed a first principal component (PC1) that explained 23.5% of variance in DNAm, and this was negatively associated with gestational age at birth. PC1 was associated with PSMD (β=0.349, p=8.37×10−10) and PSNDI (β=0.364, p=4.15×10−5), but not with PSFA (β=−0.035, p=0.510); these relationships mirrored the imaging metrics’ associations with gestational age at birth.

Gestational age at birth has a profound and widely distributed effect on the neonatal saliva methylome. Enriched gene ontology terms related to cell-cell contacts reveal pathways that could mediate the effect of early life environmental exposures on development. Finally, associations between differential DNAm and image markers of white matter tract microstructure suggest that variation in DNAm may provide a link between preterm birth and the dysconnectivity of developing brain networks that characterises atypical brain development in preterm infants.
Estimating COVID-19 infection fatality rate in Mumbai during 2020
Authors: Banaji Murad
Published: April 2021

The aim of this piece is to provide estimates of the infection fatality rate (IFR) of COVID-19 in Mumbai during 2020, namely the fraction of SARS-CoV-2 infections which resulted in death. Estimates are presented for slums and nonslum areas, and for the city as a whole. These are based largely on the city’s official COVID-19 fatality data, seroprevalence data, and all-cause mortality data. Using recorded COVID-19 fatalities in the numerator, we obtain IFR estimates of 0.13%-0.17%. On the other hand, using excess deaths we obtain IFR estimates of 0.28%-0.40%. The estimates based on excess deaths are broadly consistent with the city’s age structure, and meta-analyses of COVID-19 age-stratified IFR. If excess deaths were largely from COVID-19, then only around half of COVID-19 deaths were officially recorded in the city. The analysis indicates that levels of excess mortality in excess deaths per 1000 population were similar in the city’s slums and nonslum areas. On the other hand the estimated ratio of excess deaths to official COVID-19 deaths in the slums was much higher than in nonslum areas, suggesting much weaker COVID-19 death reporting from the slums.
Public health impacts of an imminent Red Sea oil spill
Authors: Huynh Benjamin Q , Kwong Laura H , Kiang Mathew V , Chin Elizabeth T , Mohareb Amir M , Jumaan Aisha O , Basu Sanjay , Geldsetzer Pascal , Karaki Fatima M , Rehkopf David H
Published: April 2021

The possibility of a massive oil spill in the Red Sea is increasingly likely. The Safer, a deteriorating oil tanker containing 1.1 million barrels of oil, has been deserted near the coast of Yemen since 2015, and threatens environmental catastrophe to a country presently in a humanitarian crisis. Here, we model the immediate public health impacts of a simulated spill. We estimate all of Yemen’s imported fuel through its key Red Sea ports would be disrupted, and that the anticipated spill could disrupt clean water supply equivalent to the daily use of 9 to 9.9 million people, food supply for 5.7 to 8.4 million people, and 93% to 100% of Yemen’s Red Sea fisheries. We also estimate an increased risk of cardiovascular hospitalization from pollution ranging from 5.8% to 42.0% over the duration of the spill. The spill and its potentially disastrous impacts remain entirely preventable through offloading the oil. Our results stress the need for urgent action to avert this looming disaster.
Accuracy of antigen and nucleic acid amplification testing on saliva and naopharyngeal samples for detection of SARS-CoV-2 in ambulatory care
Authors: Kernéis Solen , Elie Caroline , Fourgeaud Jacques , Choupeaux Laure , Delarue Séverine Mercier , Alby Marie-Laure , Quentin Pierre , Pavie Juliette , Brazille Patricia , Néré Marie Laure , Minier Marine , Gabassi Audrey , Gibaud Aurélien , Gauthier Sébastien , Leroy Chrystel , Voirin-Mathieu Etienne , Poyart Claire , Vidaud Michel , Parfait Béatrice , Delaugerre Constance , Tréluyer Jean-Marc , Le Goff Jérôme
Published: April 2021

Background

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the current standard diagnostic test for of coronavirus disease 2019 (COVID-19). However, the NAAT technique is lengthy and nasopharyngeal sampling requires trained personnel. Saliva NAAT represents an interesting alternative but diagnostic performances vary widely between studies.

Objective

To assess the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as compared to nasopharyngeal NAAT.

Design

Prospective participant enrollment from 19 October through 18 December 2020.

Setting

Two community COVID-19 screening centers in Paris, France.

Participants

1452 ambulatory children and adults referred for SARS-CoV-2 testing.

Interventions

NAAT on a saliva sample (performed with three different protocols for pre-processing, amplification and detection of SARS-CoV-2) and Ag testing on a nasopharyngeal sample.

Measurements

Performance of saliva NAAT and nasopharyngeal Ag testing.

Results

Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was of 94% (95% CI, 86% to 98%), 23% (CI, 14% to 35%), 94% (CI, 88% to 97%) and 96% (CI, 91% to 99%) for the nasopharyngeal Ag test and the three different protocols of saliva NAAT, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals.

Limitations

Few children (n=122, 8%) were included.

Conclusion

In the ambulatory setting, diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT seems similar to that of nasopharyngeal NAAT, subject to strict compliance with specific pre-processing and amplification protocols.

Registration number

NCT04578509

Funding Sources

French Ministry of Health and the Assistance Publique-Hôpitaux de Paris Foundation.
Predation by protists influences the temperature response of microbial communities
Authors: Rocca Jennifer D. , Yammine Andrea , Simonin Marie , Gibert Jean P.
Published: April 2021

Temperature strongly influences microbial community structure and function, which in turn contributes to the global carbon cycle that can fuel further warming. Recent studies suggest that biotic interactions amongst microbes may play an important role in determining the temperature responses of these communities. However, how microbial predation regulates these communities under future climates is still poorly understood. Here we assess whether predation by one of the most important bacterial consumers globally – protists – influences the temperature response of a freshwater microbial community structure and function. To do so, we exposed these microbial communities to two cosmopolitan species of protists at two different temperatures, in a month-long microcosm experiment. While microbial biomass and respiration increased with temperature due to shifts in microbial community structure, these responses changed over time and in the presence of protist predators. Protists influenced microbial biomass and function through effects on community structure, and predation actually reduced microbial respiration rate at elevated temperature. Indicator species and threshold indicator taxa analyses showed that these predation effects were mostly determined by phylum-specific bacterial responses to protist density and cell size. Our study supports previous findings that temperature is an important driver of microbial communities, but also demonstrates that predation can mediate these responses to warming, with important consequences for the global carbon cycle and future warming.
Neural Potts Model
Authors: Sercu Tom , Verkuil Robert , Meier Joshua , Amos Brandon , Lin Zeming , Chen Caroline , Liu Jason , LeCun Yann , Rives Alexander
Published: April 2021

Abstract

We propose the Neural Potts Model objective as an amortized optimization problem. The objective enables training a single model with shared parameters to explicitly model energy landscapes across multiple protein families. Given a protein sequence as input, the model is trained to predict a pairwise coupling matrix for a Potts model energy function describing the local evolutionary landscape of the sequence. Couplings can be predicted for novel sequences. A controlled ablation experiment assessing unsupervised contact prediction on sets of related protein families finds a gain from amortization for low-depth multiple sequence alignments; the result is then confirmed on a database with broad coverage of protein sequences.
The Expression Pattern of miR-17, −24, −124 and −145 as Diagnostic Factor for Metastatic Gastric Cancer; a Lesson from Gastric Cancer Stem cells
Authors: Yasavoli-Sharahi Hamed , Jahangiri-Tazehkand Soheil , Iranmehr Zahra , Eslahchi Changiz , Razavi Amirnader Emami , Moradi Sharif , Asl Niloofar Shayan , Memari Fereidoon , Ebrahimi Marzieh
Published: April 2021

Background

Distant metastasis of Gastric Cancer (GC) causes more than 700 000 deaths worldwide. Cancer Stem Cells (CSCs) are a subpopulation of cancer cells responsible for aggressiveness and chemoresistance in clinical settings. MicroRNAs (miRNAs) emerge as important players in regulating self-renewal and metastasis in CSCs. Understanding the role of miRNAs in CSCs offer a potential diagnostic tool for GC patients. This study is aimed to identify miRNAs that target both stemness and metastasis in gastric cancer stem cells (GCSCs) and differentially expressed in metastatic GC patients as diagnostic biomarkers for GC metastasis.

Methods

We investigate the gene expression profile of patients using the GEO database and Rstudio software. To obtain the regulatory networks and miRNAs, the STRING and miRwalk database used. The gastric cancer tissues were obtained from Iranian National Tumor Bank (INTB) to validate the results.

Results

Our results indicated three important regulatory cores affecting the immune system’s regulation, tumor progress, and metastasis. Based on the bioinformatics results, four miRNAs miR-17-5p, miR-24-3p, miR-124-3p, and miR-145-5p, were selected, and their expression pattern was evaluated in 10 patients’ metastatic tumors compared to 10 nonmetastatic tumors by real-time PCR. The expression level of mir-17, −24, and −124 was upregulated about 8, 10, 60 folds, respectively, and miR-145 was down-regulated 4.5 folds in metastatic tumors compared to nonmetastatic tumors.

Conclusion

the high expression level of miR-17, −24, −124, and low level of miR-145 in GC patients’ samples could be a potential biomarker for the presence of GCSCs and the diagnosis of metastasis.
Enhanced RhoA signaling stabilizes E-cadherin in migrating epithelial monolayers
Authors: Gupta Shafali , Duszyc Kinga , Verma Suzie , Budnar Srikanth , Liang Xuan , Gomez Guillermo A. , Marcq Philippe , Noordstra Ivar , Yap Alpha S.
Published: April 2021

Epithelia migrate as physically coherent populations of cells. Earlier studies revealed that mechanical stress accumulates in these cellular layers as they move. These stresses are characteristically tensile in nature and have often been inferred to arise when moving cells pull upon the cell-cell adhesions that hold them together. We now report that epithelial tension at adherens junctions between migrating cells also reflects an increase in RhoA-mediated junctional contractility. We find that active RhoA levels were stimulated by p114 RhoGEF at the junctions between migrating MCF-7 monolayers, and this is accompanied by increased levels of actomyosin and mechanical tension. By applying a strategy to restore active RhoA specifically at adherens junctions by manipulating its scaffold, anillin, we found that this junctional RhoA signal was necessary to stabilize junctional E-cadherin during epithelial migration. We suggest that stabilization of E-cadherin by RhoA serves to increase cell-cell adhesion against the mechanical stresses of migration.
Role of Anthropogenic drivers in altering the forest community structure in a prime tiger habitat in central India
Authors: Dasgupta Soumya , Bhattacharya Tapajit , Bhamburkar Prafulla , Kaul Rahul
Published: April 2021

Tropical forests are complex systems with heterogenous community assemblages often threatened under conservation conflicts. Herbivory and disturbances affect the diversity and species assemblages within forest patches having different disturbance regimes. We studied the change in plant community composition and structure under a disturbance gradient in the tropical dry deciduous forest of the corridor area between Nagzira-Navegaon Tiger reserve of central India. We tested the hypothesis that the plant community will change along the proximity gradient from the human settlement depending on the anthropogenic stress. We sampled 183 nested quadrat plots to collect data on species abundance and various disturbance parameters. Density, diversity, and Importance Value Index were calculated from the collected data on species abundance and girth at breast height (GBH) of individual tree species. We did multivariate analysis to assess the changes in species assemblage along the disturbance gradients. We found 76% dissimilarity between the plant communities in the three disturbance gradients from near to far from the villages perpetrated by the difference in mean abundance of species likeTectona grandis, Terminalia sp, andLargerstroemia parviflora. The anthropogenic factors significantly influence the density and diversity of tree species and regeneration classes. We found the abundance of regeneration class increased along the distance from the villages. The study intensifies the need for proper management and conservative approach to preserve the minimum diversity of the forest patches for its structural and functional contiguity as a corridor in the central India’s highly susceptible and intricate corridor framework.
Intrinsic Mechanisms in the Gating of Resurgent Na+Currents
Authors: Ransdell Joseph L. , Moreno Jonathan D. , Bhagavan Druv , Silva Jonathan R. , Nerbonne Jeanne M.
Published: April 2021

The resurgent component of the voltage-gated sodium current (INaR) is a depolarizing conductance, revealed on membrane hyperpolarizations following brief depolarizing voltage steps, which has been shown to contribute to regulating the firing properties of numerous neuronal cell types throughout the central and peripheral nervous systems. Although mediated by the same voltage-gated sodium (Nav) channels that underlie the transient and persistent Nav current components, the gating mechanisms that contribute to the generation of INaRremain unclear. Here, we characterized Nav currents in mouse cerebellar Purkinje neurons, and used tailored voltage-clamp protocols to define how the voltage and the duration of the initial membrane depolarization affect the amplitudes and kinetics of INaR. Using the acquired voltage-clamp data, we developed a novel Markov kinetic state model with parallel (fast and slow) inactivation pathways and, we show that this model reproduces the properties of the resurgent, as well as the transient and persistent, Nav currents recorded in (mouse) cerebellar Purkinje neurons. Based on the acquired experimental data and the simulations, we propose that resurgent Na+influx occurs as a result of fast inactivating Nav channels transitioning into an open/conducting state on membrane hyperpolarization, and that the decay of INaRreflects the slow accumulation of recovered/opened Nav channels into a second, alternative and more slowly populated, inactivated state. Additional simulations reveal that extrinsic factors that affect the kinetics of fast or slow Nav channel inactivation and/or impact the relative distribution of Nav channels in the fast- and slow-inactivated states, such as the accessory Navβ4 channel subunit, can modulate the amplitude of INaR.

The resurgent component of the voltage-gated sodium current (INaR) is revealed on membranehyperpolarizationsfollowing brief depolarizing voltage steps that activate the rapidly activating and inactivating, transient Nav current (INaT). To probe the mechanisms contributing to the generation and properties of INaR, we combined whole-cell voltage-clamp recordings from mouse cerebellar Purkinje neurons with computational modeling to develop a novel, blocking particle-independent, model for the gating of INaRthat involves two parallel inactivation pathways, and we show that this model recapitulates the detailed biophysical properties of INaRmeasured in mouse cerebellar Purkinje neurons.
Comprehensive-immunopeptidomics analysis reveals presentation of potential neoantigens carrying cancer driver mutations
Authors: Minegishi Yuriko , Kiyotani Kazuma , Nemoto Kensaku , Inoue Yoshikage , Haga Yoshimi , Fujii Risa , Saichi Naomi , Nagayama Satoshi , Ueda Koji
Published: April 2021

Understanding the properties of human leukocyte antigen (HLA) peptides (HLAp) is essential for cancer precision medicine, while the direct identification of HLAp from a tiny piece of clinical tissues by mass spectrometry (MS) is still confronted with technical challenges. Here, to overcome that hindrances, high-field asymmetric waveform ion mobility spectrometry (FAIMS) is introduced to conduct differential ion mobility (DIM)-MS by seamless gas-phase fractionation optimal for scarce samples. The global-immunopeptidomics analysis enables in-depth identification of 44,785 HLAp, including 2 neoantigens with KRAS-G12V and CPPED1-R228Q from stage IV colorectal cancer (CRC) tissues obtained from 17 subjects. Comparison of tissue-based personal immunopeptidome disclosed cancer-specific processing of HLAp. Since the direct identification of neoantigens from CRC tissues suggests more potential neoantigens have yet to been identified, the targeted-immunopeptidomics by screening-oriented parallel reaction monitoring (PRM) has been established and identified two more neoantigens with oncogenic KRAS. The targeted-immunopeptidomics analysis clarifies the presentation of aimed neoantigens, including neoantigens that are unpredictable by computational algorithms. The comprehensive-immunopeptidomics approach combining the FAIMS-assisted DIM-MS and the screening-oriented PRM contributes the direct and effective identification of HLAp and emerging neoantigens from clinical tissue samples, as an advanced strategy to identify the authentic and recurrent neoantigens for cancer immunotherapy.
Eosinophils are dispensable for development of MOG35-55-induced experimental autoimmune encephalomyelitis in mice
Authors: Ruppova Klara , Lim Jong-Hyung , Fodelianaki Georgia , August Avery , Neuwirth Ales
Published: April 2021

Experimental autoimmune encephalomyelitis (EAE) represents the mouse model of multiple sclerosis, a devastating neurological disorder. EAE development and progression involves the infiltration of different immune cells into the brain and spinal cord. However, less is known about a potential role of eosinophil granulocytes for EAE disease pathogenesis. In the present study, we found enhanced eosinophil abundance accompanied by increased concentration of the eosinophil chemoattractant eotaxin-1 in the spinal cord in the course of EAE induced in C57BL/6 mice by immunization with MOG35-55peptide. However, the absence of eosinophils did not affect neuroinflammation, demyelination and clinical development or severity of EAE, as assessed in ΔdblGATA1 eosinophil-deficient mice. Taken together, despite their enhanced abundance in the inflamed spinal cord during disease progression, eosinophils were dispensable for EAE development.
What is a supercoiling-sensitive gene? Insights from topoisomerase I inhibition in the Gram-negative bacteriumDickeya dadantii
Authors: Pineau Maïwenn , Shiny Martis B. , Forquet Raphaël , Baude Jessica , Villard Camille , Grand Lucie , Popowycz Florence , Soulère Laurent , Hommais Florence , Nasser William , Reverchon Sylvie , Meyer Sam
Published: April 2021

DNA supercoiling is an essential mechanism of bacterial chromosome compaction, whose level is mainly regulated by topoisomerase I and DNA gyrase. Inhibiting either of these enzymes with antibiotics leads to global supercoiling modifications and subsequent changes in global gene expression. In previous studies, genes responding to DNA relaxation induced by gyrase inhibition were categorised as “supercoiling-sensitive”. Here, we studied the opposite variation of DNA supercoiling in the phytopathogenDickeya dadantiiusing the non-marketed antibiotic seconeolitsine. We showed that the drug is active against topoisomerase I from this species, and analysed the first transcriptomic response of a Gram-negative bacterium to topoisomerase I inhibition. We find that the responding genes essentially differ from those observed after DNA relaxation, and further depend on the growth phase. We characterised these genes at the functional level, and also detected distinct patterns in terms of expression level, spatial and orientational organisation along the chromosome. Altogether, these results highlight that the supercoiling-sensitivity is a complex feature, which depends on the action of specific topoisomerases, on the physiological conditions, and on their genomic context. Based on previousin vitroexpression data of several promoters, we propose a qualitative model of SC-dependent regulation that accounts for many of the contrasting transcriptomic features observed after gyrase or topoisomerase I inhibition.
Overcoming Attenuation Bias in Regressions using Polygenic Indices: A Comparison of Approaches
Authors: van Kippersluis Hans , Biroli Pietro , Pereira Rita Dias , Galama Titus J. , Hinke Stephanie von , Meddens S. Fleur W. , Muslimova Dilnoza , Slob Eric A.W. , de Vlaming Ronald , Rietveld Cornelius A.
Published: April 2021

Measurement error in polygenic indices (PGIs) attenuates the estimation of their effects in regression models. While this measurement error shrinks with growing Genome-wide Association Study (GWAS) sample sizes, the marginal returns to bigger sample sizes are rapidly decreasing. We analyze and compare two alternative approaches to reduce measurement error: Obviously Related Instrumental Variables (ORIV) and the PGI Repository Correction (PGI-RC). Through simulations, we show that both approaches outperform the typical (meta-analysis based) PGI in terms of bias and root mean squared error. Between families, the PGI-RC performs slightly better than ORIV, unless the prediction sample is very small (N <1, 000), or when there is considerable assortative mating. Within families, ORIV is the default choice since the PGI-RC is not available in this setting. We verify the empirical validity of the simulations by predicting educational attainment (EA) and height in a sample of siblings from the UK Biobank. We show that applying ORIV between families increases the standardized effect of the PGI by 12% (height) and by 22% (EA) compared to a meta-analysis-based PGI, yet remains slightly below the PGI-RC estimates. Furthermore, within-family ORIV regression provides the tightest lower bound for the direct genetic effect, increasing the lower bound for the direct genetic effect on EA from 0.14 to 0.18, and for height from 0.54 to 0.61 compared to a meta-analysis-based PGI.