bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 vaccination status is associated with physical activity in German-speaking countries: the COR-PHYS-Q cohort study
Authors: Schwendinger F. , Boeck H. T. , Infanger D. , Faulhaber M. , Tegtbur U. , Schmidt-Trucksäss A.
Published: January 2022

Background

To examine the association between COVID-19 vaccination status and physical activity (PA), sporting behavior, as well as barriers to PA in adults in Switzerland, Germany, and Austria.

Methods

A total of 1516 adults provided complete responses to our online questionnaire sent out in August 2021. Information about self-reported PA categories, sporting behavior, barriers to PA, and COVID-19 vaccination status were gathered. Main analyses were done using multiple linear regression adjusted for relevant parameters.

Results

We found a significant association of vaccination status with total PA (p= .011), vigorous PA (p= .015), and moderate PA (p= .001) but not transport-related PA or sedentary time. Unvaccinated adults tended to have more total and vigorous PA than those vaccinated once (ratios of geometric means: 1.34 and 1.60, respectively) or twice (1.22 and 1.09, respectively). Yet, not sufficient evidence was available to confirm this. There was no between-group difference in the contribution of leisure time, work-related, or transport-related PA to total PA. Vaccination status was not associated with sporting behavior except for jogging as the primary intensive type of sports. Finally, there were no significant differences in any of the COVID-19 specific barriers to PA between groups.

Conclusion

Our data showed that vaccination status is associated with PA even in summer, where the number of COVID-19 cases was low and the severity of safety measures was mild. These findings may enhance future research and improve/extend COVID-19-specific PA guidelines.
Household composition, smoking cessation and relapse: results from a prospective longitudinal Australian cohort
Authors: Saxby Karinna , Ireland Andrew , Ghijben Peter , Sweeney Rohan , Sia Kah-Ling , Chen Esa , Farrell Michael , McRobbie Hayden , Courtney Ryan , Petrie Dennis
Published: January 2022

Aims

To examine the association between household members and their tobacco smoking behaviour on patterns of smoking cessation and relapse.

Design and participants

Data was sourced from 19 waves (years 2001 to 2019) of the nationally representative Household Income and Labour Dynamics in Australia (HILDA) survey, with all household members 15 years or older completing the survey annually. The final sample included, on average, 3,056 ex-smokers and 2,612 smokers per wave.

Measurements

Self-reported annual smoking status was used to construct measures of smoking cessation and relapse. Information on household structure and relationships was then used to develop variables describing the presence of household members and their smoking status by relationship to the individual (i.e., child, parent, spouse, sibling, or other). Multivariate regression analyses were then used to predict the likelihood of smoking cessation and relapse controlling for the presence of other household members and their smoking status, sociodemographic characteristics, number of cigarettes smoked per day, previous quit attempts, and years abstained from smoking.

Findings

Individuals that lived with non-smokers were more likely to quit [OR1.22 (95%CI 1.11;1.34)] relative to those living alone. However, this favourable association was negated if living with another smoker, which was associated with a reduced likelihood of smoking cessation [OR0.77 (95%CI 0.72;0.83)] and a higher likelihood of relapse [1.37 (95%CI 1.22;1.53)]. In particular, living with a spouse or parent that smoked reduced the likelihood of smoking cessation [OR0.71 (95%CI 0.65;0.78) and OR0.71 (95%CI 0.59;0.84), respectively] and increased the likelihood of relapse [OR1.47 (95%CI 1.28;1.69) and OR1.39 (95%CI 1.00;1.94) respectively] relative to living with their non-smoking counterparts.

Conclusions

Household composition and intrahousehold smoking behaviour should be considered when delivering, or estimating the benefits of, smoking cessation interventions. Interventions which encourage smoking cessation at the household level may assist individuals to quit and abstain from smoking.
‘I don’t know anybody who said, “oh great, let’s get measles”’: a qualitative study of responses to childhood vaccinations (MMRV) among Orthodox Jews in Jerusalem following the 2018-19 measles outbreaks
Authors: Kasstan Ben
Published: January 2022

Measles outbreaks have emerged among religious minorities in the global north, which cross regional and national boundaries and raise implications for measles elimination targets. Yet, studies are ambiguous about the reasons that underlie non-vaccination in religious populations, and whether and how religious “beliefs” influence vaccine decision-making among populations with suboptimal vaccination coverage. In 2018-19, Israel experienced the largest measles outbreaks in a quarter century – the burden of which disproportionately affected Orthodox Jewish neighbourhoods in Jerusalem. The objective of this study was to explore how Orthodox Jewish households in Jerusalem responded to the measles outbreaks in their neighbourhoods and how they viewed childhood vaccination (MMRV) during a public health emergency.

Research methods primarily consisted of 25 in-depth semi-structured interviews conducted with 23 household heads, and 2 public health professionals involved in planning and implementation of vaccination services. Thematic analysis generated five key themes, i) where the issue of sub-optimal vaccination uptake was perceived to be located; ii) how responsive people and services were to the measles outbreaks; iii) the sources of information used in vaccine decisions by religious parents; vi) whether vaccination was deemed a religious issue; and v) how vaccination influenced social relations within religious neighbourhoods.

Results demonstrate parental investment in protecting child health, with decisions around vaccination reflecting vaccine efficacy and safety, and the risk of measles transmission. Household heads across all Orthodox Jewish backgrounds were not apathetic towards measles transmission. No religious “beliefs” were identified for non-vaccination among the household heads in this cohort. Rather than relegating suboptimal vaccination uptake among religious minorities and populations as an issue of religious “beliefs,” quality social science research should examine – and clearly convey – how religion influences vaccine decision-making. Such clarity can help to avoid stigmatizing religious minorities and populations, and to plan for appropriate vaccination programmes and promotion campaigns.
dsSurvival: Privacy preserving survival models for federated individual patient meta-analysis in DataSHIELD
Authors: Banerjee Soumya , Sofack Ghislain N. , Papakonstantinou Thodoris , Avraam Demetris , Burton Paul , Zöller Daniela , Bishop Tom R.P.
Published: January 2022

Objective

Achieving sufficient statistical power in a survival analysis usually requires large amounts of data from different sites. Sensitivity of individual-level data, ethical and practical considerations regarding data sharing across institutions could be a potential challenge for achieving this added power. Hence we implemented a federated meta-analysis approach of survival models in DataSHIELD, where only anonymous aggregated data are shared across institutions, while simultaneously allowing for exploratory, interactive modelling.

In this case, meta-analysis techniques to combine analysis results from each site are a solution, but an analytic workflow involving local analysis undertaken at individual studies hinders exploration. Thus, the aim is to provide a framework for performing meta-analysis of Cox regression models across institutions without manual analysis steps for the data providers.

Results

We introduce a package (dsSurvival) which allows privacy preserving meta-analysis of survival models, including the calculation of hazard ratios. Our tool can be of great use in biomedical research where there is a need for building survival models and there are privacy concerns about sharing data.
Evaluating Human Mutation Databases for ‘Treatability’ Using Personalized Antisense Oligonucleotides
Authors: Mittal Swapnil , Tang Isaac , Gleeson Joseph G.
Published: January 2022

Genome sequencing in the clinic often allows patients to receive a molecular diagnosis. However, variants are most often evaluated for pathogenicity, neglecting potential “treatability”, and thus often yielding limited clinical benefit. Several collaborative efforts now aim to provide a therapy based upon the genetic variants, even if the drug will benefit only a single patient. Antisense oligonucleotide (ASO) therapies, among others, offer attractive “programmable” and relatively safe platforms for individualized therapy. The landscape of “ASO-treatable” variants is largely uncharted, with new developments emerging for loss-of-function (LOF), haploinsufficient, and gain-of-function (GOF) variants. ASOs can access the genome to target splice-gain variants, poison exons, untranslated/regulatory regions, and naturally-occurring antisense transcripts. Many of these approaches have yet to be proven clinically beneficial, and it is unclear if disease in some patients has progressed past the point where benefit could reasonably be expected. Here we mine public variant databases to identify potential future therapeutic targets. We found that the majority of human pathogenic genetic variants have one or more approaches that could be targeted therapeutically, advantaging the many ways that ASOs can regulate gene expression. The future might see medical teams considering “treatability” when interpreting genome sequencing results, to fully realize benefits for patients.
Stem embolism vulnerability curve depends on methods used: is there a fifth mechanism of cavitation?
Authors: Peng Guoquan , Cao Lei , Ren Zhiyang , Liang Zhao , Yu Guo , Yang Dongmei , Tyree Melvin T.
Published: January 2022

A long-established ecological paradigm predicts a functional relationship determining vulnerability to cavitation: vulnerability increases with vessel hydraulic efficiency and vessel diameter. Even within a species, big vessels cavitate before small ones.

Some centrifuge methods for measuring vulnerability are prone to artifacts due to nano-particles seeding early embolism, as the particles are drawn into vessels during measurements. Both the Sperry and Cochard rotors are prone to early cavitation due to nano-particles drawn into long and wide vessels in Robinia pseudoacacia and Quercus acutissima, whereas extraction centrifuge methods produce vulnerability curves more resistant to cavitation.

Sufficient nano-particles pass through the stems to seed early embolism in all rotor designs. For several years, people have thought that early embolism is induced by nano-particles present in laboratory water. One new hypothesis is that the origin of nano-particles is from cut-open living cells but a much bigger study including many species is required to confirm this idea. This paper confirms the hypothesis in comparisons between short-vesselled Acer, and long-vesselled Robinia, and Quercus. Our new results and a review of old results justifies bigger study.

Hypothetical nano-particles might explain why different methods for measuring vulnerability curves cause different T50 = tensions causing 50% loss of hydraulic conductivity. Hence the hypothesis for future research should be that the open-vessel artifact is consistent with ‘long’ vessels surrounded by cut open living cells.

One sentence Summary

Nano-particles induced early cavitation in species with vessel lengths about ¼ the stem length used in all centrifuge rotors, and the origin of nano-particles might be from living cells nearby vessels
Loss of pod strings in common bean is associated with gene duplication, retrotransposon insertion, and overexpression of PvIND
Authors: Parker Travis , Cetz José , de Sousa Lorenna Lopes , Kuzay Saarah , Lo Sassoum , de Oliveira Floriani Talissa , Njau Serah , Arunga Esther , Duitama Jorge , Jernstedt Judy , Myers James R. , Llaca Victor , Herrera-Estrella Alfredo , Gepts Paul
Published: January 2022

Regulation of fruit development has been central in the evolution and domestication of flowering plants. In common bean (Phaseolus vulgaris L.), a major global staple crop, the two main economic categories are distinguished by differences in fiber deposition in pods: a) dry beans with fibrous and stringy pods; and b) stringless snap/green beans with reduced fiber deposition, but which frequently revert to the ancestral stringy state. To better understand control of this important trait, we first characterized developmental patterns of gene expression in four phenotypically diverse varieties. Then, using isogenic stringless/revertant pairs of six snap bean varieties, we identified strong overexpression of the common bean ortholog of INDEHISCENT (PvIND) in non-stringy types compared to their string-producing counterparts. Microscopy of these pairs indicates that PvIND overexpression is associated with overspecification of weak dehiscence zone cells throughout the entire pod vascular sheath. No differences in PvIND DNA methylation were correlated with pod string phenotype. Sequencing of a 500 kb region surrounding PvIND in the stringless snap bean cultivar Hystyle revealed that PvIND had been duplicated into two tandem repeats, and that a Ty1-copia retrotransposon was inserted between these tandem repeats, possibly driving PvIND overexpression. Further sequencing of stringless/revertant isogenic pairs and diverse materials indicated that these sequence features had been uniformly lost in revertant types and were strongly predictive of pod phenotype, supporting their role in PvIND overexpression and pod string phenotype.

Significance

Fruit dehiscence is a key trait for seed dissemination. In legumes, e.g., common bean, dehiscence relies on the presence of fibers, including pod “strings”. Selections during domestication and improvement have decreased (dry beans) or eliminated (snap beans) fibers, but reversion to the fibrous state occurs frequently in snap beans. In this article, we document that fiber loss or gain is controlled by structural changes at the PvIND locus, a homolog of the Arabidopsis INDEHISCENT gene. These changes include a duplication of the locus and insertion/deletion of a retrotransposon, which are associated with significant changes in PvIND expression. Our findings shed light on the molecular basis of unstable mutations and provide potential solutions to an important pod quality issue.

Competing Interest Statement

The authors have no competing interests.
Dissolvable microgel-templated macroporous hydrogels for controlled cell assembly
Authors: Jiang Zhongliang , Lin Fang-Yi , Jiang Kun , Nguyen Han , Chang Chun-Yi , Lin Chien-Chi
Published: January 2022

Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.
MvPPT: a highly efficient and sensitive pathogenicity prediction tool for missense variants
Authors: Tong Shi-Yuan , Fan Ke , Zhou Zai-Wei , Liu Lin-Yun , Zhang Shu-Qing , Fu Yinghui , Wang Guang-Zhong , Zhu Ying , Yu Yong-Chun
Published: January 2022

Next generation sequencing technologies both boost the discovery of variants in the human genome and exacerbate the challenges of pathogenic variant identification. In this study, we developed mvPPT (Pathogenicity Prediction Tool for missense variants), a highly sensitive and accurate missense variant classifier based on gradient boosting. MvPPT adopts high-confidence training sets with a wide spectrum of variant profiles, and extracts three categories of features, including scores from existing prediction tools, allele, amino acid and genotype frequencies, and genomic context. Compared with established predictors, mvPPT achieved superior performance in all test sets, regardless of data source. In addition, our study also provides guidance for training set and feature selection strategies, as well as reveals highly relevant features, which may further provide biological insights of variant pathogenicity.
A blunted GPR183/oxysterol axis during dysglycemia results in delayed recruitment of macrophages to the lung during M. tuberculosis infection
Authors: Ngo Minh Dao , Bartlett Stacey , Bielefeldt-Ohmann Helle , Foo Cheng Xiang , Sinha Roma , Arachige Buddhika Jayakody , Reed Sarah , Mandrup-Poulsen Thomas , Rosenkilde Mette Marie , Ronacher Katharina
Published: January 2022

We previously reported that the oxidised cholesterol-sensing receptor GPR183 is significantly downregulated in blood from tuberculosis (TB) patients with diabetes compared to TB patients without co-morbidities and that lower GPR183 expression in blood is associated with more severe pulmonary TB on chest-x-ray consistent with observations in dysglycemic mice. To further elucidate the role of this receptor and its endogenous high affinity agonist 7α,25-di-hydroxycholesterol (7α,25-OHC) in the lung, we studied high fat diet (HFD)-induced dysglycemic mice infected with M.tuberculosis.

We found that the 7α,25-OHC-producing enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) were highly upregulated upon M. tuberculosis infection in the lungs of normoglycemic mice, and this was associated with increased expression of GPR183 indicative of effective recruitment of GPR183-expressing immune cells to the site of infection. We demonstrated that CYP7B1 was predominantly expressed by macrophages in the centre of TB granulomas. Expression of CYP7B1 was significantly blunted in lungs from HFD-fed dysglycemic animals and this coincided with delayed recruitment of macrophages to the lung during early infection and more severe lung pathology. GPR183 deficient mice similarly had reduced macrophage recruitment during early infection demonstrating a requirement of the GPR183/oxysterol axis for macrophage infiltration into the lung in TB.

Together our data demonstrate that oxidised cholesterols and GPR183 play an important role in positioning macrophages to the site of M. tuberculosis infection and that this is impaired by HFD-induced dysglycemia, adding a mechanistic explanation to the poorer TB outcomes in patients with diabetes.
Sex-specific distribution and classification ofWolbachiainfections and mitochondrial DNA haplogroups inAedes albopictusfrom the Indo-Pacific
Authors: Yang Qiong , Chung Jessica , Robinson Katie L. , Schmidt Thomas L. , Ross Perran A. , Liang Jiaxin , Hoffmann Ary A.
Published: January 2022

The arbovirus vectorAedes albopictus(Asian tiger mosquito) is common throughout the Indo-Pacific region, where most global dengue transmission occurs. We analysed population genomic data and tested for cryptic species in 160Ae. albopictussampled from 16 locations across this region. We found no evidence of crypticAe. albopictusbut found multiple intraspecific COI haplotypes partitioned into groups representing three Asian lineages: East Asia, Southeast Asia and Indonesia. Papua New Guinea (PNG), Vanuatu and Christmas Island shared recent coancestry, and Indonesia and Timor-Leste were likely invaded from East Asia. We used a machine learning trained on morphologically sexed samples to classify sexes using multiple genetic features and then characterized thewAlbA andwAlbBWolbachiainfections in 664 other samples. ThewAlbA andwAlbB infections as detected by qPCR showed markedly different patterns in the sexes. For females, most populations had a very high double infection incidence, with 67% being the lowest value (from Timor-Leste). For males, the incidence of double infections ranged from 100% (PNG) to 0% (Vanuatu). Only 6 females were infected solely by thewAlbA infection, while rare uninfected mosquitoes were found in both sexes. ThewAlbA andwAlbB densities varied significantly among populations. For mosquitoes from Torres Strait and Vietnam, thewAlbB density was similar in single-infected and superinfected (wAlbA andwAlbB) mosquitoes. There was a positive association betweenwAlbA andwAlbB infection densities in superinfectedAe. albopictus. Our findings provide no evidence of cryptic species ofAe. albopictusin the region and suggest site-specific factors influencing the incidence ofWolbachiainfections and their densities. We also demonstrate the usefulness of SNPs as sex-specific mosquito markers. The results provide baseline data for the exploitation ofWolbachia-induced cytoplasmic incompatibility (CI) in dengue control.
Toxoplasma ceramide synthases: a curious case of gene duplication, divergence and key functionality
Authors: Koutsogiannis Zisis , Mina John G. , Albus Christin A. , Kol Matthijs A. , Holthuis Joost C. M. , Pohl Ehmke , Denny Paul W.
Published: January 2022

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause foetal damage and abortion in both animals and humans. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2 and, using a conditional gene regulation approach, establish their roles in pathogenicity and parasite fitness. Interestingly, we observed that whilst TgCerS1 was a fully functional orthologue of the yeast Lag1p capable of catalysing the conversion of sphinganine to ceramide, in contrast TgCerS2 was catalytically inactive. Furthermore, genomic deletion of TgCerS1 using CRISPR/Cas-9 led to viable but slow growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of TgCerS2 was only accessible utilising the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this ‘pseudo’ ceramide synthase, TgCerS2, has an even greater role in parasite fitness than its catalytically active orthologue (TgCerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa arose through gene duplication. However, in the Apicomplexa the duplicated copy subsequently evolved into a non-functional ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites, a feature that could potentially be exploited in the development of new antiprotozoals.

Author Summary

Sphingolipids, essential and ubiquitous lipids in the Eukaryota, are both synthesized and scavenged by the parasitic apicomplexan protozoa, including Toxoplasma gondii. Ceramide is the precursor for all sphingolipids and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases TgCerS1 and TgCerS2. Surprisingly, whilst TgCerS1 was fully functional, catalysing the conversion of sphinganine to ceramide, TgCerS2 was catalytically inactive. However, we demonstrated that this ‘pseudo’ ceramide synthase has an even greater role in parasite fitness than the catalytically active TgCerS1. Phylogenetic analyses indicated that these isoforms arose through gene duplication and the duplicated copy subsequently evolved into the ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the highly unusual biology that characterizes these protozoan parasites, a feature that could potentially be exploited for the development of new antiprotozoals.
Prevalence and disease expression of pathogenic and likely pathogenic variants associated with inherited cardiomyopathies in the general population
Authors: Bourfiss Mimount , van Vugt Marion , Alasiri Abdulrahman I. , Ruijsink Bram , van Setten Jessica , Schmidt Amand F. , Dooijes Dennis , Puyol-Antón Esther , Velthuis Birgitta K. , van Tintelen J. Peter , te Riele Anneline S.J.M. , Baas Annette F. , Asselbergs Folkert W.
Published: January 2022

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200,643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analysed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analysed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251 and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared to controls, cardiovascular mortality was higher in DCM G+ (OR 1.67 [95% CI 1.04;2.59], p=0.030), but similar in ARVC and HCM G+ (p≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (OR 3.66 [95% CI 2.24;5.81], p=4.9×10−7) and HCM G+ (OR 3.03 [95% CI 1.98;4.56], p=5.8×10−7), but comparable in ARVC G+ (p=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (p=3.3×10−4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (p=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.
Effect of Vaccination on Household Transmission of SARS-CoV-2 Delta VOC
Authors: Lyngse Frederik Plesner , Mølbak Kåre , Denwood Matt , Christiansen Lasse Engbo , Møller Camilla Holten , Rasmussen Morten , Cohen Arieh Sierrah , Stegger Marc , Fonager Jannik , Sieber Raphael , Ellegaard Kirsten , Nielsen Claus , Kirkeby Carsten Thure
Published: January 2022

1

The SARS-CoV-2 Delta variant of concern (VOC), which has shown increased transmission compared with previous variants, emerged rapidly globally during the first half of 2021, and became one of the most widespread SARS-CoV-2 variants worldwide. We utilized total population data from 24,693 Danish households with 53,584 potential secondary cases to estimate household transmission of the Delta VOC in relation to vaccination status. We found that the vaccine effectiveness against susceptibility (VES) was 61% (95%-CI: 59-63) and that the vaccine effectiveness against transmissibility (VET) was 42% (95%-CI: 39-45). We also found that unvaccinated individuals with an infection exhibited a higher viral load (one third of a standard deviation) compared to fully vaccinated individuals with a breakthrough infection. Our results imply that vaccinations reduce susceptibility as well as transmissibility. The results are important for policy makers to select strategies for reducing transmission of SARS-CoV-2.
Applying Machine Learning and AI Explanations to Analyze Vaccine Hesitancy
Authors: Lange Carsten , Lange Jian
Published: January 2022

The paper identifies and quantifies the impact of race, poverty, politics, and age on COVID-19 vaccination rates in counties across the continental US. Both traditional Ordinary Least Square (OLS) regression analysis and Random Forest machine learning algorithms are applied to quantify contributing factors for county-level vaccination hesitancy. With the machine learning model, joint effects of multiple variables (race/ethnicity, partisanship, age etc.) are considered simultaneously to capture the unique combination of what factors affect the vaccination rate. By implementing a state-of-the-art Artificial Intelligence Explanations (AIX) algorithm, it is possible to solve the black box problem with machine learning models and provide answers to the "how much" question for each measured impact factor in every county.

For most counties a higher percentage vote for Republicans, a greater African American population share, and a higher poverty rate lower the vaccination rate. While a higher Asian population share increases the predicted vaccination rate. The impact on the vaccination rate from the Hispanic population proportion is positive in the OLS model, but only positive for counties with very high Hispanic population (65% and more) in the Random Forest model. Both the proportion of seniors and the one for young people in a county have a significant impact in the OLS model - positive and negative, respectively. In contrast, the impacts are ambiguous in the Random Forest model.

Because results vary between geographies and since the AIX algorithm is able to quantify vaccine impacts individually for each county, this research can be tailored to local communities. This way it is a helpful tool for local health officials and other policymakers to improve vaccination rates.

An interactive online mapping dashboard that identifies impact factors for individual U.S. counties is available at https://www.cpp.edu/~clange/vacmap.html. It is apparent that the influence of impact factors is not universally the same across different geographies.
Persistence of endogenous SARS-CoV-2 and pepper mild mottle virus RNA in wastewater settled solids
Authors: Roldan-Hernandez Laura , Graham Katherine E. , Duong Dorothea , Boehm Alexandria B.
Published: January 2022

Limited information is available on the decay rate of endogenous SARS-CoV-2 and pepper mild mottle virus (PMMoV) RNA in wastewater and primary settled solids, potentially limiting an understanding of how transit or holding times within wastewater infrastructure might impact RNA measurements and their relationship to community COVID-19 infections. In this study, primary settled solids samples were collected from two wastewater treatment plants in the San Francisco Bay Area. Samples were thoroughly mixed, aliquoted into subsamples, and stored at 4°C, 22°C, and 37 °C for 10 days. The concentration of SARS-CoV-2 (N1 and N2 targets) and PMMoV RNA was measured using an RT-ddPCR. Limited decay (< 1 log10 reduction) was observed in the detection of viral RNA targets at all temperature conditions, suggesting that SARS-CoV-2 and PMMoV RNA can be highly persistent in solids. First-order decay rate constants ranged from 0.011 - 0.098 day-1 for SARS-CoV-2 RNA and 0.010 - 0.091 day-1 for PMMoV RNA, depending on temperature conditions. Slower decay was observed for SARS-CoV-2 RNA in primary settled solids compared to previously reported decay in wastewater influent. Further research is needed to understand if solid content and wastewater characteristics might influence the persistence of viral RNA targets.

Synopsis

SARS-CoV-2 and PMMoV genomic RNA is highly stable in wastewater settled solids over 10 days at several environmentally relevant temperatures.

Abstract Figure
PhysiBoSS 2.0: a sustainable integration of stochastic Boolean and agent-based modelling frameworks
Authors: Ponce-de-Leon Miguel , Montagud Arnau , Noel Vincent , Pradas Gerard , Meert Annika , Barillot Emmanuel , Calzone Laurence , Valencia Alfonso
Published: January 2022

Cancer progression is a complex phenomenon that spans multiple scales from molecular to cellular and intercellular. Simulations can be used to perturb the underlying mechanisms of those systems and to generate hypotheses on novel therapies. We present a new version of PhysiBoSS, a multiscale modelling framework designed to cover multiple temporal and spatial scales, that improves its integration with PhysiCell, decoupling the cell agent simulations with the internal Boolean model in an easy-to-maintain computational framework. PhysiBoSS 2.0 is a redesign and reimplementation of PhysiBoSS, conceived as an add-on that expands the PhysiCell agent-based functionalities with intracellular cell signalling using MaBoSS having a decoupled, maintainable and model-agnostic design. PhysiBoSS 2.0 successfully reproduces simulations reported in the former version and expands its functionalities such as using user-defined models and cells' specifications, having mechanistic submodels of substrate internalisation with ODEs and enabling the study of drug synergies. PhysiBoSS 2.0 is open-source and publicly available on GitHub (https://github.com/PhysiBoSS/PhysiBoSS) under the BSD 3-clause license with several repositories of accompanying interoperable tools. Additionally, a nanoHUB tool has been set up to ease the use of PhysiBoSS 2.0 (https://nanohub.org/tools/pba4tnf/).
RETINOBLASTOMA RELATED (RBR) interaction with key factors of the RNA-directed DNA methylation (RdDM) pathway
Authors: Jesús León-Ruiz , Annie Espinal-Centeno , Ikram Blilou , Ben Scheres , Mario Arteaga-Vázquez , Alfredo Cruz-Ramírez
Published: January 2022

Transposable elements and other repetitive elements are silenced by the RNA-directed DNA methylation pathway (RdDM). In RdDM, POLIV-derived transcripts are converted into double stranded RNA (dsRNA) by the activity of RDR2 and subsequently processed into 24 nucleotide short interfering RNAs (24 -nt siRNAs) by DCL3. 24-nt siRNAs are recruited by AGO4 and serve as guides to direct AGO4 - siRNA complexes to chromatin bound POLV-derived transcripts generated from the template/target DNA. The interaction between POLV, AGO4, DMS3, DRD1, RDM1 and DRM2 promotes DRM2-mediated de novo DNA methylation.

The Arabidopsis Retinoblastoma protein homolog is a master regulator of cell cycle, stem cell maintenance and development. In silico exploration of RBR protein partners revealed that several members of the RdDM pathway contain a motif that confers high affinity binding to RBR, including the largest subunits of POLIV and POLV (NRPD1 and NRPE1), the shared second largest subunit of POLIV and POLV (NRPD/E2), RDR1, RDR2, DCL3, DRM2 and SUVR2. We demonstrate that RBR binds to DRM2, DRD1 and SUVR2. We also report that seedlings from loss -of-function mutants in RdDM and in RBR show similar phenotypes in the root apical meristem. Furthermore, we show that RdDM and SUVR2 targets are up-regulated in the 35S::AmiGO-RBR background.

Our results suggest a novel mechanism for RBR function in transcriptional gene silencing based on the interaction with key players of the RdDM pathway and opens several new hypotheses, including the convergence of RBR-DRM2 on the transcriptional control of TEs and several cell/tissue and stage -specific target genes.
Machine learning-assisted identification of factors contributing to the technical variability between bulk and single-cell RNA-seq experiments
Authors: Lipnitskaya Sofya , Shen Yang , Legewie Stefan , Klein Holger , Becker Kolja
Published: January 2022

Background

Recent studies in the area of transcriptomics performed on single-cell and population levels reveal noticeable variability in gene expression measurements provided by different RNA sequencing technologies. Due to increased noise and complexity of single-cell RNA-Seq (scRNA-Seq) data over the bulk experiment, there is a substantial number of variably-expressed genes and so-called dropouts, challenging the subsequent computational analysis and potentially leading to false positive discoveries. In order to investigate factors affecting technical variability between RNA sequencing experiments of different technologies, we performed a systematic assessment of single-cell and bulk RNA-Seq data, which have undergone the same pre-processing and sample preparation procedures.

Results

Our analysis indicates that variability between gene expression measurements as well as dropout events are not exclusively caused by biological variability, low expression levels, or random variation. Furthermore, we propose FAVSeq, a machine learning-assisted pipeline for detection of factors contributing to gene expression variability in matched RNA-Seq data provided by two technologies. Based on the analysis of the matched bulk and single-cell dataset, we found the 3’-UTR and transcript lengths as the most relevant effectors of the observed variation between RNA-Seq experiments, while the same factors together with cellular compartments were shown to be associated with dropouts.

Conclusions

Here, we investigated the sources of variation in RNA-Seq profiles of matched single-cell and bulk experiments. In addition, we proposed the FAVSeq pipeline for analyzing multimodal RNA sequencing data, which allowed to identify factors affecting quantitative difference in gene expression measurements as well as the presence of dropouts. Hereby, the derived knowledge can be employed further in order to improve the interpretation of RNA-Seq data and identify genes that can be affected by assay-based deviations. Source code is available under the MIT license at https://github.com/slipnitskaya/FAVSeq.
Reconstructing Kinetic Models for Dynamical Studies of Metabolism using Generative Adversarial Networks
Authors: Choudhury Subham , Moret Michael , Salvy Pierre , Weilandt Daniel , Hatzimanikatis Vassily , Miskovic Ljubisa
Published: January 2022

Kinetic models of metabolic networks relate metabolic fluxes, metabolite concentrations, and enzyme levels through well-defined mechanistic relations rendering them an essential tool for systems biology studies aiming to capture and understand the behavior of living organisms. However, due to the lack of information about the kinetic properties of enzymes and the uncertainties associated with available experimental data, traditional kinetic modeling approaches often yield only a few or no kinetic models with desirable dynamical properties making the computational analysis unreliable and computationally inefficient. We present REKINDLE (REconstruction of KINetic models using Deep LEarning), a deep-learning-based framework for efficiently generating large-scale kinetic models with dynamic properties matching the ones observed in living organisms. We showcase REKINDLE’s efficiency and capabilities through three studies where we: (i) generate large populations of kinetic models that allow reliablein silicotesting of hypotheses and systems biology designs, (ii) navigate the phenotypic space by leveraging the transfer learning capability of generative adversarial networks, demonstrating that the generators trained for one physiology can be fine-tuned for another physiology using a low amount of data, and (iii) expand upon existing datasets, making them amenable to thorough computational biology and data-science analyses. The results show that data-driven neural networks assimilate implicit kinetic knowledge and structure of metabolic networks and generate novel kinetic models with tailored properties and statistical diversity. We anticipate that our framework will advance our understanding of metabolism and accelerate future research in health, biotechnology, and systems and synthetic biology. REKINDLE is available as an open-access tool.
HIGH FREQUENCY ROOT DYNAMICS: SAMPLING AND INTERPRETATION USING REPLICATED ROBOTIC MINIRHIZOTRONS
Authors: Nair Richard , Strube Martin , Hertel Martin , Kolle Olaf , Rolo Victor , Migliavacca Mirco
Published: January 2022

Automating dynamic fine root data collection in the field is a longstanding challenge with multiple applications for co-interpretation and synthesis for ecosystem understanding. High frequency root data are only achievable with paired automated sampling and processing. However, automatic minirhizotron (root camera) instruments are still rare and data is often not collected in natural soils nor analysed at high temporal resolution. Instruments must also be affordable for replication and robust under variable natural conditions.

Here, we show a system built with off-the-shelf parts which samples at sub-daily resolution. We paired this with a neural network to analyse all images collected. We performed two mesocosm studies and two field trials alongside ancillary data collection (soil CO2efflux, temperature and moisture content, and ‘PhenoCam’-derived above-ground dynamics. We produce robust daily time-series of root dynamics under all conditions. Temporal root changes were a stronger driver than absolute biomass on soil CO2efflux in mesocosm. Proximal sensed above ground dynamics and belowground from minirhizotron data were not synchronised. Root properties extracted were sensitive to soil moisture and occasionally to time of day (potentially relating to soil moisture). This may only affect high frequency imagery and should be considered in interpreting such data.

HIGHLIGHT

Completely automatic root dynamics with method transferrable between field settings.
Chromosome-scale assembly of the highly heterozygous genome of red clover (Trifolium pratense L.), an allogamous forage crop species
Authors: Bickhart Derek M. , Koch Lisa M. , Smith Timothy P.L. , Riday Heathcliffe , Sullivan Michael L.
Published: January 2022

Red clover (Trifolium pratense L.) is used as a forage crop due to a variety of favorable traits relative to other crops. Improved varieties have been developed through conventional breeding approaches, but progress could be accelerated and gene discovery facilitated using modern genomic methods. Existing short-read based genome assemblies of the ~420 Megabase (Mb) genome are fragmented into >135,000 contigs with numerous errors in order and orientation within scaffolds, likely due to the biology of the plant which displays gametophytic self-incompatibility resulting in inherent high heterozygosity. A high-quality long-read based assembly of red clover is presented that reduces the number of contigs by more than 500-fold, improves the per-base quality, and increases the contig N50 statistic by three orders of magnitude. The 413.5 Mb assembly is nearly 20% longer than the 350 Mb short read assembly, closer to the predicted genome size. Quality measures are presented and full-length isoform sequence of RNA transcripts reported for use in assessing accuracy and for future annotation of the genome. The assembly accurately represents the seven main linkage groups present in the genome of an allogamous (outcrossing), highly heterozygous plant species.
Estimating dynamic individual coactivation patterns based on densely sampled resting-state fMRI data and utilizing it for better subject identification
Authors: Yang Hang , Yao Xing , Zhang Hong , Meng Chun , Biswal Bharat
Published: January 2022

As a complex dynamic system, the brain exhibits spatially organized recurring patterns of activity over time. Coactivation patterns (CAPs), which analyzes data from each single frame, has been utilized to detect transient brain activity states recently. However, previous CAP analyses have been conducted at the group-level, which might neglect meaningful individual differences. Here, we estimate individual CAP states at both subject- and scan-level based on a densely-sampled dataset: Midnight Scan Club. We used differential identifiability, which measures the gap between intra- and intersubject similarity, to evaluate individual differences. We found individual CAPs at the subject-level achieved the best discrimination ability by maintaining high intra-subject similarity and enlarging inter-subject differences, and brain regions of association networks mainly contributed to the identifiability. On the other hand, scan-level CAP states were unstable across scans for the same participant. Expectedly, we found subject-specific CAPs became more reliable and discriminative with more data (i.e., longer duration). As the acquisition time of each participant is limited in practice, our results recommend a data collection strategy that collects more scans with appropriate duration (e.g., 12~15 mins/scan) to obtain more reliable subject-specific CAPs, when total acquisition time is fixed (e.g., 150 mins). Overall, this work has constructed reliable subject-specific CAP states with meaningful individual differences and provides a starting point for the subsequent applications of individual brain dynamics.
Ghost lineages can invalidate or even reverse findings regarding gene flow
Authors: Tricou Théo , Tannier Eric , de Vienne Damien M.
Published: January 2022

Introgression, endosymbiosis and gene transfer, i.e. Horizontal Gene Flow (HGF), are primordial sources of innovation in all domains of life. Our knowledge on HGF relies on detection methods that exploit some of its signatures left on extant genomes. One of them is the effect of HGF on branch lengths of constructed phylogenies. This signature has been formalized in statistical tests for HGF detection, and used for example to detect massive adaptive gene flows in malaria vectors or to order evolutionary events involved in eukaryogenesis. However these studies rely on the assumption that ghost lineages (all unsampled extant and extinct taxa) have little influence. We demonstrate here with simulations and data re-analysis, that when considering the more realistic condition that unsampled taxa are legion compared to sampled ones, the conclusion of these studies become unfounded or even reversed. This illustrates the necessity to recognize the existence of ghosts in evolutionary studies.