bluuebunny/crossref_metadata_2025 huggingface dataset:
Topological data analysis identifies distinct biomarker phenotypes during the ‘inflammatory’ phase of COVID-19
Authors: Blair Paul W. , Brandsma Joost , Chenoweth Josh , Richard Stephanie A. , Epsi Nusrat J. , Mehta Rittal , Striegel Deborah , Clemens Emily G. , Lindholm David A. , Maves Ryan C. , Larson Derek T. , Mende Katrin , Colombo Rhonda E. , Ganesan Anuradha , Lalani Tahaniyat , Colombo Christopher J , Malloy Allison A. , Snow Andrew L. , Schully Kevin L. , Lanteri Charlotte , Simons Mark P. , Dumler John S. , Tribble David , Burgess Timothy , Pollett Simon , Agan Brian K. , Clark Danielle V. ,   the EPICC COVID-19 Cohort Study Group
Published: December 2021

OBJECTIVES

The relationships between baseline clinical phenotypes and the cytokine milieu of the peak ‘inflammatory’ phase of coronavirus 2019 (COVID-19) are not yet well understood. We used Topological Data Analysis (TDA), a dimensionality reduction technique to identify patterns of inflammation associated with COVID-19 severity and clinical characteristics.

DESIGN

Exploratory analysis from a multi-center prospective cohort study.

SETTING

Eight military hospitals across the United States between April 2020 and January 2021.

PATIENTS

Adult (≥18 years of age) SARS-CoV-2 positive inpatient and outpatient participants were enrolled with plasma samples selected from the putative ‘inflammatory’ phase of COVID-19, defined as 15-28 days post symptom onset.

INTERVENTIONS

None.

MEASUREMENTS AND MAIN RESULTS

Concentrations of 12 inflammatory protein biomarkers were measured using a broad dynamic range immunoassay. TDA identified 3 distinct inflammatory protein expression clusters. Peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated with logistic regression for associations with each cluster. The study population (n=129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct clusters were found that differed by peak disease severity (p <0.001), age (p <0.001), BMI (p<0.001), and CCI (p=0.001).

CONCLUSIONS

Exploratory clustering methods can stratify heterogeneous patient populations and identify distinct inflammation patterns associated with comorbid disease, obesity, and severe illness due to COVID-19.
Interpretable and Predictive Deep Modeling of the SARS-CoV-2 Spike Protein Sequence
Authors: Sokhansanj Bahrad A. , Zhao Zhengqiao , Rosen Gail L.
Published: December 2021

As the COVID-19 pandemic continues, the SARS-CoV-2 virus continues to rapidly mutate and change in ways that impact virulence, transmissibility, and immune evasion. Genome sequencing is a critical tool, as other biological techniques can be more costly, time-consuming, and difficult. However, the rapid and complex evolution of SARS-CoV-2 challenges conventional sequence analysis methods like phylogenetic analysis. The virus picks up and loses mutations independently in multiple subclades, often in novel or unexpected combinations, and, as for the newly emerged Omicron variant, sometimes with long explained branches. We propose interpretable deep sequence models trained by machine learning to complement conventional methods. We apply Transformer-based neural network models developed for natural language processing to analyze protein sequences. We add network layers to generate sample embeddings and sequence-wide attention to interpret models and visualize multiscale patterns. We demonstrate and validate our framework by modeling SARS-CoV-2 and coronavirus taxonomy. We then develop an interpretable predictive model of disease severity that integrates SARS-CoV-2 spike protein sequence and patient demographic variables, using publicly available data from the GISAID database. We also apply our model to Omicron. Based on knowledge prior to the availability of empirical data for Omicron, we predict: 1) reduced neutralization antibody activity (15-50 fold) greater than any previously characterized variant, varying between Omicron sublineages, and 2) reduced risk of severe disease (by 35-40%) relative to Delta. Both predictions are in accord with recent epidemiological and experimental data.
Relationship between temperature and relative humidity on the initial spread of COVID-19 cases and deaths in Brazil
Authors: Anselmo Olinto Maria Teresa , Garcez Anderson , Brunelli Gabriel , Olinto Flávio Anselmo , Fanton Marcos , Canuto Raquel
Published: December 2021

Introduction

Climate conditions may have influence on the transmission of COVID-19. Thus, this study aims to evaluate the impact of temperature and relative humidity on COVID-19 cases and deaths during the initial phase of the epidemic in Brazil.

Methodology

This is an ecological study based on secondary data. Daily data on new COVID-19 cases and deaths and on climate indicators was collected from February 20th to April 18th, 2020 (n=59 days), for all state capital cities in Brazil and the Federal District (Brasília). The studied climate indicators included mean temperature, temperature amplitude, mean relative humidity, relative humidity amplitude, and percentage of days with mean relative humidity less than or equal to 65%. Correlation and multiple linear regression analysis were performed for all cities and was also stratified by quintiles of the COVID-19 incidence rate.

Results

Mean daily temperature was positively correlated with the number of days until the first COVID-19 case was reported. A lower mean relative humidity was correlated with lower number of cases and deaths in Brazil, especially when the relative humidity was less than or equal to 65%. Higher temperatures and humidity amplitudes were correlated with lower COVID-19 mortality. Additionally, after controlling for humidity, cumulative cases of COVID-19 were inversely associated with temperature in cities with mean temperatures less than 25.8 °C.

Conclusions

Our findings indicate that variations in temperature and humidity across the Brazilian territory may have influenced the spread of the novel coronavirus during the initial phase of the epidemic in the country.
Vitamin D Status & Latitude Predict Brain Lesions in Adrenoleukodystrophy
Authors: van Haren Keith , Wilkes Jacob , Moser Ann B. , Raymond Gerald V. , Richardson Troy , Aubourg Patrick , Collins Timothy W. , Mowry Ellen M , Bonkowsky Joshua L.
Published: December 2021

A subset of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions. Risk factors are largely undefined. We used two independent cohorts to assess whether low vitamin D status predicts lesion development. In our first cohort, we measured 25-hydroxyvitamin D in 53 plasma samples from 20 pre-lesional ALD boys followed at two centers; half subsequently developed lesions. In our second cohort, we measured latitude (using home ZIP code) among 230 ALD boys in a database of 51 US pediatric hospitals; over half developed lesions. In regression models, low plasma vitamin D and northerly latitudes independently predicted ALD brain lesions.
COVID-19 in children in NSW, Australia, during the 2021 Delta outbreak: Severity and Disease spectrum
Authors: Williams Phoebe , Koirala Archana , Saravanos Gemma , Lopez Laura , Glover Catherine , Sharma Ketaki , Williams Tracey , Carey Emma , Shaw Nadine , Dickins Emma , Sitaram Neela , Ging Joanne , Bray Paula , Crawford Nigel , McMullan Brendan , Macartney Kristine , Wood Nicholas , Fulton Beth , Lau Christine , Britton Philip N
Published: December 2021

Objective(s)

To describe the severity and clinical spectrum of SARS-CoV-2 infection in Australian children during the 2021 Delta outbreak.

Design, Setting & Participants

A prospective cohort study of children <16 years with a positive SARS-CoV-2 nucleic acid test cared for by the Sydney Children’s Hospital Network (SCHN) virtual and inpatient medical teams between 1 June – 31 October 2021.

Main outcome measures

Demographic and clinical data from all admitted patients and a random sample of outpatients managed under the SCHN virtual care team were analysed to identify risk factors for admission to hospital.

Results

There were 17,474 SARS-CoV-2 infections in children <16 years in NSW during the study period, of whom 11,985 (68.6%) received care coordinated by SCHN. Twenty one percent of children infected with SARS-CoV-2 were asymptomatic. For every 100 SARS-CoV-2 infections in children <16 years, 1.26 (95% CI 1.06 to 1.46) required hospital admission for medical care; while 2.46 (95% CI 2.18 to 2.73) required admission for social reasons only. Risk factors for hospitalisation for medical care included age <6 months, a history of prematurity, age 12 to <16 years, and a history of medical comorbidities (aOR 7.23 [95% CI 2.92 to 19.4]). Of 17,474 infections, 15 children (median age 12.8years) required ICU admission; and 294 children required hospital admission due to social or welfare reasons.

Conclusion

The majority of children with SARS-CoV-2 infection (Delta variant) had asymptomatic or mild disease. Hospitalisation was uncommon and occurred most frequently in young infants and adolescents with comorbidities. More children were hospitalised for social reasons than for medical care.
Divergent SARS CoV-2 Omicron-specific T- and B-cell responses in COVID-19 vaccine recipients
Authors: GeurtsvanKessel Corine H. , Geers Daryl , Schmitz Katharina S. , Mykytyn Anna Z. , Lamers Mart M , Bogers Susanne , Gommers Lennert , Sablerolles Roos S.G. , Nieuwkoop Nella N. , Rijsbergen Laurine C. , van Dijk Laura L.A. , de Wilde Janet , Alblas Kimberley , Breugem Tim I. , Rijnders Bart J.A. , de Jager Herbert , Weiskopf Daniela , van der Kuy P. Hugo M. , Sette Alessandro , Koopmans Marion P.G. , Grifoni Alba , Haagmans Bart L. , de Vries Rory D.
Published: December 2021

The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses to SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers (HCW) after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays with authentic virus showed consistent cross-neutralization of the Beta and Delta variants in study participants, but Omicron-specific responses were significantly lower or absent (up to a 34-fold decrease compared to D614G). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV.2 priming partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to D614G. CD4+ T-cell responses were detected up to 6 months after all vaccination regimens; S-specific T-cell responses were highest after mRNA-1273 vaccination. No significant differences were detected between D614G- and variant-specific T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations may be needed to further restore Omicron cross-neutralization by antibodies.
Waning of SARS-CoV-2 booster viral-load reduction effectiveness
Authors: Levine-Tiefenbrun Matan , Yelin Idan , Alapi Hillel , Herzel Esma , Kuint Jacob , Chodick Gabriel , Gazit Sivan , Patalon Tal , Kishony Roy
Published: December 2021

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs), an important factor affecting infectiousness. This viral-load protective effect has been waning with time post the second vaccine and later restored with a booster shot. It is currently unclear though for how long this regained effectiveness lasts. Analyzing Ct values of SARS-CoV-2 qRT-PCR tests of over 22,000 infections during a Delta-variant-dominant period in Israel, we found that this viral-load reduction effectiveness significantly declines within months post the booster dose. Adjusting for age, sex and calendric date, Ct values of RdRp gene initially increased by 2.7 [CI: 2.3-3.0] relative to unvaccinated in the first month post the booster dose, yet then decayed to a difference of 1.3 [CI: 0.7-1.9] in the second month and became small and insignificant in the third to fourth months. The rate and magnitude of this post-booster decline in viral-load reduction effectiveness mirror those observed post the second vaccine. These results suggest rapid waning of the booster’s effectiveness in reducing infectiousness, possibly affecting community-level spread of the virus.
SARS-CoV-2 Omicron variant: exploring healthcare workers’ awareness and perception of vaccine effectiveness: a national survey during the first week of WHO variant alert
Authors: Temsah Mohamad-Hani , Aljamaan Fadi , Alenezi Shuliweeh , Alhasan Khalid , Alrabiaah Abdulkarim , Assiri Rasha , Bassrawi Rolan , Alhaboob Ali , Alshahrani Fatimah , Alarabi Mohamad , Alaraj Ali , Alharbi Nasser S , Halwani Rabih , Jamal Amr , Al-Eyadhy Ayman , AbdulMajeed Naif , Alfarra Lina , Almashdali Wafa , Al-Zamil Fahad , Barry Mazin , Memish Ziad A. , Al-Tawfiq Jaffar A. , Alsubaie Sarah
Published: December 2021

Background

As the SARS-CoV2 Omicron variant spreads in several countries, healthcare workers’ (HCWs) perceptions and worries regarding vaccine effectiveness and boosters warrant reassessment.

Methods

An online questionnaire among HCWs in Saudi Arabia (KSA) was distributed from Dec 1st to 6th 2021 to assess their perceptions, vaccine advocacy to the Omicron variant, and their perception of the effectivness of infection prevention measures and vaccination to prevent its spread, their Omicron variant related worries in comparison to the other variants, and their agreement with mandatory vaccination in general for adults.

Results

Among the 1285 HCW participants, two-thirds were female, 49.8 % were nurses, 46.4% were physicians, and 50.0% worked in tertiary care hospitals. 66.9% considered vaccination to be the most effective way to prevent the spread of the Omicron variant and future variants. The respondents however perceived social distancing (78.0%), universal masking (77.8%), and avoiding unnecessary travel (71.4%) as slightly superior to vaccination to prevent the spread of SARS-CoV-2 variants. HCWs aging 55 or older agreed singficanlty with vaccine ineffictivness to control Omicron spread, while those who believed in non-pharmacolgical infection prevention measures agreed signifcantly with vaccination for that purpose. Male HCWs had a significant agreement with mandatory vaccination of all eligible adult populations. On the other hand, unwilling HCWs to receive the vaccine had strong disagreements with mandatory vaccination.

Conclusions

The current study in the first week of Omicron showed that only two-thirds of HCWs felt that vaccination was the best option to prevent the spread of the Omicron variant, indicating the need for further motivation campaigns for vaccination and booster dose. HCWs had a strong belief in infection prevention measures to contain the spread of SARS-CoV-2 variants that should be encouraged and augmented.
Sociodemographic factors and self-restraint from social behaviors during the COVID-19 pandemic in Japan: a cross-sectional study
Authors: Mori Takahiro , Nagata Tomohisa , Ikegami Kazunori , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa , Mori Koji ,   for the CORoNaWork project
Published: December 2021

The control of human flow has led to better control of COVID-19 infections. Japan’s state of emergency, unlike other countries, is not legally binding but is rather a request for individual self-restraint; thus, factors must be identified that do not respond to self-restraint, and countermeasures considered for those factors to enhance its efficacy. We examined the relationship between sociodemographic factors and self-restraint toward going out in public during a pandemic in Japan. This cross-sectional study used data for February 18–19, 2021, obtained from an internet survey; 19,560 participants aged 20–65 were included in the analysis. We identified five relevant behaviors: (1) taking a day trip; (2) eating out with five people or more; (3) gathering with friends and colleagues; (4) shopping for other than daily necessities; (5) shopping for daily necessities. Multilevel logistic regression analyses were used to examine the association between sociodemographic factors and self-restraint for each of the behaviors. Results showed that for behaviors other than shopping for daily necessities, women, those aged 60–65, married people, highly educated people, high-income earners, desk workers and those who mainly work with interpersonal communication, and those with underlying disease reported more self-restraint. Older people had less self-restraint than younger people toward shopping for daily necessities; an underlying disease had no effect on the identified behavior. Specialized interventions for these groups that include recommendations for greater self-restraint may improve the efficacy of the implementing measures that request self-restraint.
Effects of Covid-19 on the human central olfactory system: a natural pre-post experiment
Authors: Thunell Evelina , Peter Moa G. , Lenoir Vincent , Andersson Patrik , Landis Basile N. , Becker Minerva , Lundström Johan N.
Published: December 2021

Reduced olfactory function is the symptom with the highest prevalence in COVID-19 with nearly 70% of individuals with COVID-19 experiencing partial or total loss of their sense of smell at some point during the disease. The exact cause is not known but beyond peripheral damage, studies have demonstrated insults to both the olfactory bulb and central olfactory brain areas. However, these studies often lack both baseline pre-COVID-19 assessments and a control group and could therefore simply reflect preexisting risk factors. Right before the COVID-19 outbreak, we completed an olfactory focused study including structural MR brain images and a full clinical olfactory test. Opportunistically, we invited participants back one year later, including 9 participants who had experienced mild to medium COVID-19 (C19+) and 12 that had not (C19-), thereby creating a pre-post controlled natural experiment with a control group. Despite C19+ participants reporting subjective olfactory dysfunction, few showed signs of objectively altered function one year later. Critically, all but one individual in the C19+ group had reduced olfactory bulb volume with an average volume reduction of 14.3%, but this did not amount to a significant between group difference compared to the control group (2.3% reduction) using inference statistics. No morphological differences in cerebral olfactory areas were found but we found stronger functional connectivity between olfactory brain areas in the C19+ croup at the post measure. Taken together, these data suggest that COVID-19 might cause a long-term reduction in olfactory bulb volume but with no discernible differences in cerebral olfactory regions.
Evolution of COVID-19 Health Disparities in Arizona
Authors: Shen Felix L. , Shu Jingmin , Lee Matthew , Oh Hyunsung , Marsiglia Flavio , Li Ming , Runger George , Liu Li
Published: December 2021

Objective

COVID-19 burdens are disproportionally high in underserved and vulnerable groups in Arizona. As the pandemic progresses, it is unclear if the disparities have evolved. In this study, we aim to elicit the dynamic landscape of COVID-19 disparities at the community level and identify newly emerged vulnerable subpopulations.

Materials and Methods

We compiled biweekly COVID-19 case counts of 274 zip code tabulation areas (ZCTAs) in Arizona from October 21, 2020, to November 25, 2021, during which the COVID-19 growth rate has changed significantly. Within each growth period, we detected health disparities by testing associations between the growth rate of COVID-19 cases in a ZCTA and the population composition of race/ethnicity, income, employment, and age. We then compared the associations between periods to discover temporal patterns of health disparities.

Results

High percentage of Latinx or Black residents, high poverty rate, and young median age were risk factors of high cumulative COVID-19 case counts in a ZCTA. However, the impact of these factors on the growth rate of new COVID-19 cases varied. While high percentage of Black residents and young median age remained as risk factors of fast COVID-19 growth rate, high poverty rate became a protective factor. The association between the percentage of Latinx residents and the COVID-19 growth rate converted from positive to negative during summer 2021. The unemployment rate emerged as a new risk factor of fast COVID-19 growth rate after September 2021. Based on these findings, we identified 37 ZCTAs that are highly vulnerable to fast escalation of COVID-19 cases.

Discussion and Conclusion

As the pandemic progresses, disadvantaged communities continue suffering from escalated risk of COVID-19 infection. But the vulnerabilities have evolved. While the disparities related to Latinx ethnicity improved gradually, those related to Black ethnicity and young communities aggravated. The struggle of financially disadvantaged communities continued, although the burden had shifted from those living under the poverty line to those with a high unemployment rate. It is necessary to adjust current resource allocations and design and deploy new interventions to address emerging needs.
Design of Epitope Based Peptide Vaccine against Brucella Abortus OmpW Family Protein using Immunoinformatics
Authors: Elhag Mustafa , Abdelmoneim Abdelrahman Hamza , Sati Anfal Osama , Saadaldin Moaaz Mohammed , Ahmad Nagla Mohammad , Hassan Mohammed A.
Published: December 2021

Brucella abortus is a small aerobic, non-spore-forming, non-motile intracellular coccobacilli localized in the reproductive organs of host animals and causes acute or chronic disorders. It infects approximately 200 cases per 100,000 of the population and has become endemic in many countries. OmpW family protein is an outer membrane protein involved in the initial interaction between the pathogen and it’s host. This study predicts an effective epitope-based vaccine against OmpW family protein of Brucella abortus using immunoinformatics tools. Sequences were obtained from NCBI and prediction tests were accomplished to analyze possible epitopes for B and T cells. Seven B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Forty-three MHC I epitopes were the most promising, while 438 from MHC II. For the population coverage, the epitopes covered 99.97% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove it’s effectiveness.
Genome assembly, transcriptome and SNP database for chum salmon (Oncorhynchus keta)
Authors: Rondeau Eric B. , Christensen Kris A. , Sakhrani Dionne , Biagi Carlo A. , Wetklo Mike , Johnson Hollie A. , Despins Cody A. , Leggatt Rosalind A. , Minkley David R. , Withler Ruth E. , Beacham Terry D. , Koop Ben F. , Devlin Robert H.
Published: December 2021

Chum salmon (Oncorhynchus keta) is the species with the widest geographic range of the anadromous Pacific salmonids,. Chum salmon is the second largest of the Pacific salmon, behind Chinook salmon, and considered the most plentiful Pacific salmon by overall biomass. This species is of significant commercial and economic importance: on average the commercial chum salmon fishery has the second highest processed value of the Pacific salmon within British Columbia. The aim of this work was to establish genomic baseline resources for this species. Our first step to accomplish this goal was to generate a chum salmon reference genome assembly from a doubled-haploid chum salmon. Gene annotation of this genome was facilitated by an extensive RNA-seq database we were able to create from multiple tissues. Range-wide resequencing of chum salmon genomes allowed us to categorize genome-wide geographic variation, which in turn reinforced the idea that genetic differentiation was best described on a regional, rather than at a stock-specific, level. Within British Columbia, chum salmon regional groupings were described at the conservation unit (CU) level, and there may be substructure within particular CUs. Genome wide associations of phenotypic sex to SNP genetic markers identified two clear peaks, a very strong peak on Linkage Group 15, and another on Linkage Group 3. With these new resources, we were better able to characterize the sex-determining region and gain further insights into sex determination in chum salmon and the general biology of this species.
Recommendations for clinical interpretation of variants found in non-coding regions of the genome
Authors: Ellingford Jamie M , Ahn Joo Wook , Bagnall Richard D , Baralle Diana , Barton Stephanie , Campbell Chris , Downes Kate , Ellard Sian , Duff-Farrier Celia , FitzPatrick David R , Ingles Jodie , Krishnan Neesha , Lord Jenny , Martin Hilary C , Newman William G , O’Donnell-Luria Anne , Ramsden Simon C , Rehm Heidi L , Richardson Ebony , Singer-Berk Moriel , Taylor Jenny C , Williams Maggie , Wood Jordan C , Wright Caroline F , Harrison Steven M , Whiffin Nicola
Published: December 2021

Purpose

The majority of clinical genetic testing focuses almost exclusively on regions of the genome that directly encode proteins. The important role of variants in non-coding regions in penetrant disease is, however, increasingly being demonstrated, and the use of whole genome sequencing in clinical diagnostic settings is rising across a large range of genetic disorders. Despite this, there is no existing guidance on how current guidelines designed primarily for variants in protein-coding regions should be adapted for variants identified in other genomic contexts.

Methods

We convened a panel of clinical and research scientists with wide-ranging expertise in clinical variant interpretation, with specific experience in variants within non-coding regions. This panel discussed and refined an initial draft of the guidelines which were then extensively tested and reviewed by external groups.

Results

We discuss considerations specifically for variants in non-coding regions of the genome. We outline how to define candidate regulatory elements, highlight examples of mechanisms through which non-coding region variants can lead to penetrant monogenic disease, and outline how existing guidelines can be adapted for these variants.

Conclusion

These recommendations aim to increase the number and range of non-coding region variants that can be clinically interpreted, which, together with a compatible phenotype, can lead to new diagnoses and catalyse the discovery of novel disease mechanisms.
Vaccine effectiveness against hospital admission in South African health care workers who received a homologous booster of Ad26.COV2 during an Omicron COVID19 wave: Preliminary Results of the Sisonke 2 Study
Authors: Gray Glenda E , Collie Shirley , Garrett Nigel , Goga Ameena , Champion Jared , Zylstra Matthew , Reddy Tarylee , Yende Nonhlanhla , Seocharan Ishen , Takalani Azwi , Sanne Ian , Mayat Fatima , Odhiambo Jacky , Bamford Lesley , Moultrie Harry , Fairall Lara , Bekker Linda-Gail
Published: December 2021

Following the results of the ENSEMBLE 2 study, which demonstrated improved vaccine efficacy of a two-dose regimen of Ad26.COV.2 vaccine given 2 months apart, we expanded the Sisonke study which had provided single dose Ad26.COV.2 vaccine to almost 500 000 health care workers (HCW) in South Africa to include a booster dose of the Ad26.COV.2. Sisonke 2 enrolled 227 310 HCW from the 8 November to the 17 December 2021. Enrolment commenced before the onset of the Omicron driven fourth wave in South Africa affording us an opportunity to evaluate early VE in preventing hospital admissions of a homologous boost of the Ad26.COV.2 vaccine given 6-9 months after the initial vaccination in HCW.

We estimated vaccine effectiveness (VE) of the Ad26.COV2.S vaccine booster in 69 092 HCW as compared to unvaccinated individuals enrolled in the same managed care organization using a test negative design. We compared VE against COVID19 admission for omicron during the period 15 November to 20 December 2021. After adjusting for confounders, we observed that VE for hospitalisation increased over time since booster dose, from 63% (95%CI 31-81%); to 84% (95% CI 67-92%) and then 85% (95% CI: 54-95%), 0-13 days, 14-27 days, and 1-2 months post-boost.

We provide the first evidence of the effectiveness of a homologous Ad26.COV.2 vaccine boost given 6-9 months after the initial single vaccination series during a period of omicron variant circulation. This data is important given the increased reliance on the Ad26.COV.2 vaccine in Africa.
Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine (BBV152) in children from 2 to 18 years of age: an open-label, age-de-escalation phase 2/3 study
Authors: Vadrevu Krishna Mohan , Reddy Siddharth , Jogdand Harsh , Ganneru Brunda , Mirza Nizam , Tripathy V.N. , Singh Chandramani , Khalatkar Vasant , Prasanth Siddaiah , Rai Sanjay , Ella Raches , Blackwelder William , Prasad Sai , Ella Krishna
Published: December 2021

Background

We assessed the safety, reactogenicity, and immunogenicity of BBV152 in an open-label age de-escalation study in three age cohorts of children from 18 years of age down to 2 years of age.

Methods

This was a phase 2/3 open-label, multi-centre study done across six hospitals in India. All children received two 0.5mL doses of BBV152 (Covaxin®, Bharat Biotech International Ltd., Hyderabad, India), which is the same formulation indicated in adults. Participants were monitored for adverse events, and post-vaccination blood draws were collected to assess neutralising antibodies. A total of 526 children were enrolled into Group 1 (ages 12 through 18 years, n=176), Group 2 (ages 6 through 12 years, n=175), Group 3 (ages 2 through 6 years, n=175).

Findings

There were no serious adverse events, deaths, or withdrawals due to an adverse event during the study. Vaccination with BBV152 was generally well tolerated, with no substantial difference in reactogenicity profiles between the different age groups. Similar immune responses were measured as microneutralisation (MNT) antibody titers in all three age groups. Vaccine-induced MNT responses in all groups were comparable to BEI reference sera run in the same assay. Seroconversion (measured by Plaque Reduction Neutralization Test (PRNT)) achieved high levels (95-98%) in all three groups four weeks after the second vaccination. The PRNT GMT ratio was 1·76 (95%CI: 1.32 – 2.33) (GMT all children subgroup / GMT in adults) had a lower limit ≥ 1, indicating superior antibodies in children when compared to adults. Vaccine responses were skewed towards a Th1 response with IgG1/IgG4 ratios above 1.

Interpretation

BBV152 is well tolerated and immunogenic in children from 18 years down to 2 years of age. Immunogenicity analysis (by PRNT) shows superior antibody responses were observed in children compared to adults, suggesting that BBV152 will also be efficacious in this age group.
Neutralizing antibody responses to SARS-CoV-2: a population based seroepidemiological analysis in Delhi, India
Authors: Sharma Pragya , Gupta Ekta , Basu Saurav , Aggarwal Reshu , Mishra Suruchi , Kale Pratibha , Mundeja Nutan , Charan B S , Singh Gautam Kumar , Singh Mongjam Meghachandra
Published: December 2021

We conducted this study to estimate seroprevalence of neutralizing antibodies in the general population and to further correlate it with the IgG SARS-CoV-2 IgG levels. This present cross-sectional analysis was conducted as a sequel to a state level community-based seroepidemiological study in Delhi, India. A total of 2564 seropositive samples were selected from 25622 seropositive samples through simple random sampling. Neutralizing capacity was estimated by performing a surrogate virus neutralization test with the sVNT (GenScript) assay. Neutralizing antibody against the SARS-CoV-2 virus was operationally considered as detected when the signal inhibition was ≥30%.

A total of 2233 (87.1%, 95% C.I. 85.7, 88.3) of the 2564 SARS-CoV-2 seropositive samples had detectable neutralizing antibodies. On bi-variate analysis but not on adjusted analysis, Covid-19 vaccination showed a statistically significant association with the presence of neutralizing antibodies (p<0.001). The signal/ cut off (S/CO) of SARS-CoV-2 IgG ranged from 1.00 to 22.8 (median 11.40). In samples with S/CO ≥4.00, the neutralizing antibodies ranged from 94.5 to 100%, while in samples with S/CO <4.00, it ranged from 52.0 to 79.2%. The neutralizing antibody seroprevalence strongly correlated with the S/CO range (r=0.62, p=0.002). In conclusion, in populations with high SARS-CoV-2 seroprevalence, neutralizing antibodies are generated in nearly 9 of 10 seropositive individuals.
SoyFGB v2.0: a unique access to variations of Chinese Soybean Gene Bank (CNSGB) germplasm
Authors: Zheng Tianqing , Li Yinghui , Li Yanfei , Zhang Shengrui , Wang Chunchao , Zhang Fan , Zhang Lina , Wu Xiangyun , Tian Yu , Jiang Shan , Xu Jianlong , Qiu Lijuan
Published: December 2021

In Chinese National Soybean GeneBank (CNSGB), we have collected more than 30,000 soybean accessions. However, data sharing for soybean remains an especially ‘sensitive’ question, and how to share the genome variations within rule frame has been bothering the soybean germplasm workers for a long time.

Here we release a big data source named Soybean Functional Genomics & Breeding database (SoyFGB v2.0) (https://sfgb.rmbreeding.cn/), which embed a core collection of 2,214 soybean resequencing genome (2K-SG) from the CNSGB germplasm. This source presents a unique example which may help elucidating the following three major functions for multiple genome data mining with general interests for plant researchers. 1) On-line analysis tools are provided by the ‘Analysis’ module for haplotype mining in high-throughput genotyped germplasms with different methods. 2) Variations for 2K-SG are provided in SoyFGB v2.0 by Browse module which contains two functions of ‘SNP’ and ‘InDel’. Together with the ‘Gene (SNP & InDel)’ function embedded in Search module, the genotypic information of 2K-SG for targeting gene / region is accessible. 3) Scaled phenotype data of 42 traits, including 9 quality and 33 quantitative traits are provided by SoyFGB v2.0. With the scaled-phenotype data search and seed request tools under a control list, the germplasm information could be shared without direct downloading the unpublished phenotypic data or information of sensitive germplasms.

In a word, the mode of data mining and sharing underlies SoyFGB v2.0 may inspire more ideas for works on genome resources of not only soybean but also the other plants.
Perception and propagation of activity through the cortical hierarchy is determined by neural variability
Authors: Rowland James M. , van der Plas Thijs L. , Loidolt Matthias , Lees Robert M. , Keeling Joshua , Dehning Jonas , Akam Thomas , Priesemann Viola , Packer Adam M.
Published: December 2021

The brains of higher organisms are composed of anatomically and functionally distinct regions performing specialised tasks; but regions do not operate in isolation. Orchestration of complex behaviours requires communication between brain regions, but how neural activity dynamics are organised to facilitate reliable transmission is not well understood. We studied this process directly by generating neural activity that propagates between brain regions and drives behaviour, allowing us to assess how populations of neurons in sensory cortex cooperate to transmit information. We achieved this by imaging two hierarchically organised and densely interconnected regions, the primary and secondary somatosensory cortex (S1 and S2) in mice while performing two-photon photostimulation of S1 neurons and assigning behavioural salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation signal, but also by the variability of S1 neural activity. Therefore, maximising the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability in cortex is critical to facilitate activity propagation and perception. Further, we show that propagated, behaviourally salient activity elicits balanced, persistent, and generalised activation of the downstream region. Hence, our work adds to existing understanding of cortical function by identifying how population activity is formatted to ensure robust transmission of information, allowing specialised brain regions to communicate and coordinate behaviour.
Increased resistance of SARS-CoV-2 Omicron Variant to Neutralization by Vaccine-Elicited and Therapeutic Antibodies
Authors: Tada Takuya , Zhou Hao , Dcosta Belinda M. , Samanovic Marie I. , Chivukula Vidya , Herati Ramin S. , Hubbard Stevan R. , Mulligan Mark J. , Landau Nathaniel R.
Published: December 2021

Currently authorized vaccines for SARS-CoV-2 have been highly successful in preventing infection and lessening disease severity. The vaccines maintain effectiveness against SARS-CoV-2 Variants of Concern but the heavily mutated, highly transmissible Omicron variant poses an obstacle both to vaccine protection and monoclonal antibody therapies. Analysis of the neutralization of Omicron spike protein-pseudotyped lentiviruses showed a 26-fold relative resistance (compared to D614G) to neutralization by convalescent sera and 26-34-fold resistance to Pfizer BNT162b2 and Moderna vaccine-elicited antibodies following two immunizations. A booster immunization increased neutralizing titers against Omicron by 6-8-fold. Previous SARS-CoV-2 infection followed by vaccination resulted in the highest neutralizing titers against Omicron. Regeneron REGN10933 and REGN10987, and Lilly LY-CoV555 and LY-CoV016 monoclonal antibodies were ineffective against Omicron, while Sotrovimab was partially effective. The results highlight the benefit of a booster immunization in providing protection against Omicron but demonstrate the challenge to monoclonal antibody therapies.
Precise measurement of nanoscopic septin ring structures in deep learning-assisted quantitative superresolution microscopy
Authors: Zehtabian Amin , Müller Paul Markus , Goisser Maximilian , Obendorf Leon , Jänisch Lea , Hümpfer Nadja , Rentsch Jakob , Ewers Helge
Published: December 2021

The combination of image analysis and fluorescence superresolution microscopy methods allows for unprecedented insight into the organization of macromolecular assemblies in cells. Advances in deep learning-based object recognition enables the automated processing of large amounts of data, resulting in high accuracy through averaging. However, while the analysis of highly symmetric structures of constant size allows for a resolution approaching the dimensions of structural biology, deep learning methods are prone to different forms of bias. A biased recognition of structures may prohibit the development of readouts for processes that involve significant changes in size or shape of amorphous macromolecular complexes. What is required to overcome this problem is a detailed investigation of potential sources of bias and the rigorous testing of trained models using real or simulated data covering a wide dynamic range of possible results. Here we combine single molecule localization-based superresolution microscopy of septin ring structures with the training of several different deep learning models for a quantitative investigation of bias resulting from different training approaches and finally quantitative changes in septin ring structures. We find that trade-off exists between measurement accuracy and the dynamic range of recognized phenotypes. Using our trained models, we furthermore find that septin ring size can be explained by the number of subunits they are assembled from alone. Our work provides a new experimental system for the investigation of septin polymerization.
Thermal sensitivity and seasonal change in the gut microbiome of a desert ant, Cephalotes rohweri
Authors: McMunn Marshall S. , Hudson Asher I. , Zemenick Ash T. , Egerer Monika , Philpott Stacy M. , Vannette Rachel L.
Published: December 2021

Microorganisms within ectotherms must withstand the variable body temperatures of their hosts. Shifts in host body temperature resulting from climate change have the potential to shape ectotherm microbiome composition. Microbiome compositional changes occurring in response to temperature in nature have not been frequently examined, restricting our ability to predict microbe-mediated ectotherm responses to climate change. In a set of field-based observations, we characterized gut bacterial communities and thermal exposure across a population of desert arboreal ants (Cephalotes rohweri). In a paired growth chamber experiment, we exposed ant colonies to variable temperature regimes differing by 5 °C for three months. We found that the abundance and composition of ant-associated bacteria were sensitive to elevated temperatures in both field and laboratory experiments. We observed a subset of taxa that responded similarly to temperature in the experimental and observational study, suggesting a role of seasonal temperature and local temperature differences amongst nests in shaping microbiomes within the ant population. Bacterial mutualists in the genus Cephalotococcus (Opitutales: Opitutaceae) were especially sensitive to change in temperature—decreasing in abundance in naturally warm summer nests and warm growth chambers. We also report the discovery of a member of the Candidate Phlya Radiation (Phylum: Gracilibacteria), a suspected epibiont, found in low abundance within the guts of this ant species.
Ret loss-of-function decreases neural crest progenitor proliferation and restricts developmental fate potential during enteric nervous system development
Authors: Vincent Elizabeth , Chatterjee Sumantra , Cannon Gabrielle H. , Auer Dallas , Ross Holly , Chakravarti Aravinda , Goff Loyal A.
Published: December 2021

The receptor tyrosine kinase gene RET plays a critical role in the fate specification of enteric neural crest-derived cells (ENCDCs) during enteric nervous system (ENS) development. Pathogenic RET loss of function (LoF) alleles are associated with Hirschsprung disease (HSCR), which is marked by aganglionosis of the gastrointestinal (GI) tract. ENCDCs invade the developing GI tract, proliferate, migrate caudally, and differentiate into all of the major ENS cell types. Although the major phenotypic consequences and the underlying transcriptional changes from Ret LoF in the developing ENS have been described, its cell type and state-specific effects are unknown. Consequently, we performed single- cell RNA sequencing (scRNA-seq) on an enriched population of ENCDCs isolated from the developing GI tract of Ret null heterozygous and homozygous mouse embryos at embryonic day (E)12.5 and E14.5. We demonstrate four significant findings: (1) Ret-expressing ENCDCs are a heterogeneous population composed of ENS progenitors as well as glial and neuronal committed cells; (2) neurons committed to a predominantly inhibitory motor neuron developmental trajectory are not produced under Ret LoF, leaving behind a mostly excitatory motor neuron developmental program; (3) HSCR-associated and Ret gene regulatory network genes exhibit distinct expression patterns across Ret-expressing ENCDC with their expression impacted by Ret LoF; and (4) Ret deficiency leads to precocious differentiation and reduction in the number of proliferating ENS precursors. Our results support a model in which Ret contributes to multiple distinct cellular phenotypes associated with the proper development of the ENS, including the specification of inhibitory neuron subtypes, cell cycle dynamics of ENS progenitors, and the developmental timing of neuronal and glial commitment.

Summary Statement

Ret LoF affects proper development of the mouse ENS through multiple distinct cellular phenotypes including restriction of neuronal fate potential, disruption of ENCDC migration, and modulation of progenitor proliferation rate.
A transient apical extracellular matrix relays cytoskeletal patterns to shape permanent acellular ridges on the surface of adult C. elegans
Authors: Katz Sophie S. , Barker Trevor J. , Maul-Newby Hannah M. , Sparacio Alessandro P. , Nguyen Ken C.Q. , Maybrun Chloe L. , Belfi Alexandra , Cohen Jennifer D. , Hall David H. , Sundaram Meera V. , Frand Alison R.
Published: December 2021

Apical extracellular matrices can form protruding structures such as denticles, ridges, scales, or teeth on the surfaces of epithelia. The mechanisms that shape these structures remain poorly understood. Here, we show how the actin cytoskeleton and a provisional matrix work together to sculpt acellular longitudinal alae ridges in the cuticle of adult C. elegans. Transient actomyosin-dependent constriction of the underlying lateral epidermis accompanies deposition of the provisional matrix at the earliest stages of alae formation. Actin is required to pattern the provisional matrix into longitudinal bands that are initially offset from the pattern of longitudinal actin filaments. These bands appear ultrastructurally as alternating regions of adhesion and separation within laminated provisional matrix layers. The provisional matrix is required to establish these demarcated zones of adhesion and separation, which ultimately give rise to alae ridges and their intervening valleys, respectively. Provisional matrix proteins shape the alae ridges and valleys but are not present within the final structure. We propose a morphogenetic mechanism wherein cortical actin patterns are relayed mechanically to the laminated provisional matrix to set up distinct zones of matrix layer separation and accretion that shape a permanent and acellular matrix structure.
Thresholding Approach For Low-Rank Correlation Matrix Based On Mm Algorithm
Authors: Tanioka Kensuke , Furotani Yuki , Hiwa Satoru
Published: December 2021

Background

Low-rank approximation is used for interpreting the features of a correlation matrix using visualization tools; however, a low-rank approximation may result in estimation that is far from zero even if the corresponding original value is zero. In such a case, the results lead to a misinterpretation.

Methods

To overcome this, we propose a novel approach to estimate a sparse low-rank correlation matrix based on threshold values. We introduce a new cross-validation function to tune the corresponding threshold values. To calculate the value of a function, the MM algorithm is used to estimate the sparse low-rank correlation matrix, and a grid search was performed to select the threshold values.

Results

Through numerical simulation, we found that the false positive rate (FPR) and average relative error of the proposed method were superior to those of the tandem approach. For the application of microarray gene expression, the FPRs of the proposed approach withd= 2, 3, and 5 were 0.128, 0.139, and 0.197, respectively, whereas the FPR of the tandem approach was 0.285.

Conclusions

We propose a novel approach to estimate sparse low-rank correlation matrices. The advantage of the proposed method is that it provides results that are interpretable through the use of a heatmap, thereby avoiding result misinterpretations. We demonstrated the superiority of the proposed method through both numerical simulations and real examples.