bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the distribution of phylogenetic networks generated under a birth-death-hybridization process
Authors: Justison Joshua A. , Heath Tracy A.
Published: November 2022

Gene-flow processes such as hybridization and introgression play important roles in shaping diversity across the tree of life. Recent studies extending birth-death models have made it possible to investigate patterns of reticulation in a macroevolutionary context. These models allow for different macroevolutionary patterns of gene flow events that can either add, maintain, or remove lineages—with the gene flow itself possibly being dependent on the relatedness between species—thus creating complex diversification scenarios. Further, many reticulate phylogenetic inference methods assume specific reticulation structures or phylogenies belonging to certain network classes. However, the distributions of phylogenetic networks under reticulate birth-death processes are poorly characterized, and it is unknown whether they violate common methodological assumptions. We use simulation techniques to explore phylogenetic network space under a birth-death-hybridization process where the hybridization rate can have a linear dependence on genetic distance. Specifically, we measured the number of lineages through time and role of hybridization in diversification along with the proportion of phylogenetic networks that belong to commonly used network classes (e.g., tree-child, tree-based, or level-1 networks). We find that the growth of phylogenetic networks and class membership are largely affected by assumptions about macroevolutionary patterns of gene flow. In accordance with previous studies, a lower proportion of networks belonged to these classes based on type and density of reticulate events. However, under a birth-death-hybridization process, these factors form an antagonistic relationship; the type of reticulation events that cause high membership proportions also lead to the highest reticulation density, consequently lowering the overall proportion of phylogenies in some classes. Further, we observed that genetic distance–dependent gene flow and incomplete sampling increase the proportion of class membership, primarily due to having fewer reticulate events. Our results can inform studies if their biological expectations of gene flow are associated with evolutionary histories that satisfy the assumptions of current methodology and aid in finding phylogenetic classes that are relevant for methods development.
Rockfish: A Transformer-based Model for Accurate 5-Methylcytosine Prediction from Nanopore Sequencing
Authors: Stanojević Dominik , Li Zhe , Foo Roger , Šikić Mile
Published: November 2022

DNA methylation plays a crucial role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine (5mC) which is present in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing (WGBS) successfully detect 5mC DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present Rockfish, a deep learning algorithm that significantly improves read-level 5mC detection by using Nanopore sequencing. Compared to other methods based on Nanopore sequencing, there is an increase in the single-base accuracy and the F1 measure of up to 5% and 12%, respectively. Furthermore, Rockfish shows a high correlation with WGBS and requires lower read depth while being computationally efficient. We deem that Rockfish is broadly applicable to study 5mC methylation in diverse organisms and disease systems to yield biological insights.
Genetic and structural data on the SARS-CoV-2 Omicron BQ.1 variant reveal its low potential for epidemiological expansion
Authors: Scarpa Fabio , Sanna Daria , Benvenuto Domenico , Borsetti Alessandra , Azzena Ilenia , Casu Marco , Fiori Pier Luigi , Giovanetti Marta , Maruotti Antonello , Ceccarelli Giancarlo , Caruso Arnaldo , Caccuri Francesca , Cauda Roberto , Cassone Antonio , Pascarella Stefano , Ciccozzi Massimo
Published: November 2022

The BQ.1 SARS-CoV-2 variant, also known as Cerberus, is one of the most recent Omicron descendant lineages. Compared to its direct progenitor BA.5, BQ.1 carries out some additional spike mutations in some key antigenic site which confer it further immune escape ability over other circulating lineage. In such a context, here we performed a genome-based survey aimed to obtain an as complete as possible nuance of this rapidly evolving Omicron subvariant. Genetic data suggests that BQ.1 represents an evolutionary blind background, lacking of the rapid diversification which is typical of a dangerous lineage. Indeed, the evolutionary rate of BQ.1 is very similar to that of BA.5 (7.6 × 10−4and 7 × 10−4subs/site/year, respectively), which is circulating by several months. Bayesian Skyline Plot reconstruction, indicates low level of genetic variability, suggesting that the peak has been reached around September 3, 2022. Structure analyses performed by comparing the properties of BQ.1 and BA.5 RBD indicated that the impact of the BQ.1 mutations on the affinity for ACE2 may be modest. Likewise, immunoinformatic analyses showed modest differences between the BQ.1 and the BA5 potential B-cells epitope. In conclusion, genetic and structural analysis on SARS-CoV-2 BQ.1 suggest that, it does not show evidence about its particular dangerous or high expansion capability. The monitoring genome-based must continue uninterrupted for a better understanding of its descendant and all other lineages.
Comparison of phylogenetic placements to pairwise alignments for taxonomic assignment of ciliate OTUs
Authors: Ewers Isabelle , Rajter Lubomír , Czech Lucas , Mahé Frédéric , Stamatakis Alexandros , Dunthorn Micah
Published: November 2022

Taxonomic assignment of OTUs is an important bioinformatics step in analyzing environmental sequencing data. Pairwise-alignment and phylogenetic-placement methods represent two alternative approaches to taxonomic assignments, but their results can differ. Here we used available colpodean ciliate OTUs from forest soils to compare the taxonomic assignments of VSEARCH (which performs pairwise alignments) and EPA-ng (which performs phylogenetic placements). We showed that when there are differences in taxonomic assignments between pairwise alignments and phylogenetic placements at the subtaxon level, there is a low pairwise similarity of the OTUs to the reference database. We then showcase how the output of EPA-ng can be further evaluated using GAPPA to assess the taxonomic assignments when there exist multiple equally likely placements of an OTU, by taking into account the sum over the likelihood weights of the OUT placements within a subtaxon, and the branch distances between equally likely placement locations. We also inferred evolutionary and ecological characteristics of the colpodean OTUs using their placements within subtaxa. This study demonstrates how to fully analyse the output of EPA-ng, by using GAPPA in conjunction with knowledge of the taxonomic diversity of the clade of interest.
Co-occurrence of essential gene dispensability and bypass suppressor mutations across species
Authors: Pons Carles , Leeuwen Jolanda van
Published: November 2022

Genes have been historically classified as either essential or non-essential based on their requirement for viability. However, some genes are essential in some genetic backgrounds but non-essential in others, thus challenging the binary classification of gene essentiality. Such dispensable essential genes represent a valuable model for understanding the incomplete penetrance of loss-of-function mutations that is often observed in natural populations. Here, we compiled data from multiple studies on essential gene dispensability inSaccharomyces cerevisiaeto comprehensively characterize these genes. In analyses spanning different evolutionary time-scales, ranging fromS. cerevisiaestrains to human cell lines, dispensable essential genes exhibited distinct phylogenetic properties compared to other essential and non-essential genes. Integration of interactions with suppressor genes that can bypass the gene essentiality revealed the high functional modularity of the bypass suppression network. Furthermore, dispensable essential and bypass suppressor gene pairs reflected simultaneous changes in the mutational landscape ofS. cerevisiaestrains. Importantly, species in which dispensable essential genes were non-essential tended to carry bypass suppressor mutations in their genomes. Overall, our study offers a comprehensive view of dispensable essential genes and illustrates how their interactions with bypass suppressor genes reflect evolutionary outcomes.
The CUT&RUN Blacklist of Problematic Regions of the Genome
Authors: Nordin Anna , Zambanini Gianluca , Pagella Pierfrancesco , Cantù Claudio
Published: November 2022

Cleavage Under Targets and Release Using Nuclease (CUT&RUN) is an increasingly popular technique to map genome-wide binding profiles of histone modifications, transcription factors and co-factors. The ENCODE project and others have compiled blacklists for ChIP-seq which have been widely adopted: these lists contain regions of high and unstructured signal, regardless of cell type or protein target. While CUT&RUN obtains similar results to ChIP-seq, its biochemistry and subsequent data analyses are different. We found that this results in a CUT&RUN-specific set of undesired high-signal regions. For this reason, we have compiled blacklists based on CUT&RUN data for the human and mouse genomes, identifying regions consistently called as peaks in negative controls by the CUT&RUN peak caller SEACR. Using published CUT&RUN data from our and other labs, we show that the CUT&RUN blacklist regions can persist even when peak calling is performed with SEACR against a negative control, and after ENCODE blacklist removal. Moreover, we experimentally validated the CUT&RUN Blacklists by performing reiterative negative control experiments in which no specific protein is targeted, showing that they capture >80% of the peaks identified. We propose that removing these problematic regions prior to peak calling can substantially improve the performance of SEACR-based peak calling in CUT&RUN experiments, resulting in more reliable peak datasets.
Molecular autism research in Africa: a scoping review comparing publication outputs to Brazil, India, the UK, and the USA
Authors: Frickel Emma , Bam Sophia , Buchanan Erin , Mahony Caitlyn , van der Watt Mignon , O’Ryan Colleen
Published: November 2022

The increased awareness of autism spectrum disorders (ASD) is accompanied by burgeoning ASD research, and concerted research efforts are trying to elucidate the molecular ASD aetiology. However, much of this research is concentrated in the Global North, with recent reviews of research in Sub-Saharan Africa (SSA) highlighting the significant shortage of ASD publications from this region. The most limited focus area was molecular research with only two molecular studies ever published from SSA, both being from South Africa (SA). We examine the molecular ASD research publications from 2016 to 2021 from all African countries, with a special focus on SA. The SSA publications are compared to Brazil and India, two non-African, low-to-middle-income countries (LMICs), and to the UK and USA, two high-income countries (HICs). There were 228 publications across all regions of interest; only three publications were from SA. Brazil (n=29) and India (n=27) had almost 10 times more publications than SA. The HICs had more publications than the LMICs, with the UK (n=62) and the USA (n=74) having approximately 20 to 25 times more publications than SA, respectively. Given that SA has substantial research capacity as demonstrated by its recent research on SARS-CoV-2, we explore potential reasons for this deficit in molecular ASD publications from SA. We compare mental health research outputs, GDP per capita, research and development expenditure, and the number of psychiatrists and child psychiatrists per 100,000 people across all regions. The UK and the USA had significantly higher numbers for all these indicators, consistent with their higher publication output. Among the LMICs, SA can potentially produce more molecular ASD research, however, there are numerous barriers that need to be addressed to facilitate increased research capacity. These include cultural stigmas, challenges in accessing mental healthcare, shortages of specialists in the public sector, and the unreliability of ASD diagnostic tools across the 11 official SA languages. The unique genetic architecture of African populations presents an untapped reservoir for finding novel genetic loci associated with ASD. Therefore, addressing the disparity in molecular ASD research between the Global North and SSA is integral to global advancements in ASD research.
Generative modeling of short, disordered proteins with homogeneous sequence composition
Authors: Taneja Ishan , Lasker Keren
Published: November 2022

Protein design has seen remarkable progress in the past decade, with numerous examples ofde novoproteins with novel topologies and functions being successfully synthesized. Computational tools have played a large role in the ability to rationally design proteins. Recently, there have been numerous successes applying deep learning techniques to protein design that have demonstrated comparable or significantly improved performance over traditional energy-based approaches. However, the protein design problem has been less well explored for disordered proteins or, more generally, proteins with conformational heterogeneity. In this work, we demonstrate that if one approximates the spatial output of a coarse-grained molecular dynamics simulation as a multivariate normal distribution parameterized by a mean vector (representing an ensemble-averaged pairwise distance map) and covariance matrix, one can train a generative model to learn the distribution of these parameters across a set of sequences. Specifically, we encoded the mean vector and covariance matrix for each sequence in a low-dimensional space via a fixed linear transformation and trained a masked auto-encoder to accurately learn the distribution of this low-dimensional output. Furthermore, by sampling from the masked auto-encoder and transforming the generated samples back into their original high-dimensional space, one can generate realistic, ensemble-averaged pairwise distance maps. These results were demonstrated on coarse-grained simulation data derived from approximately 2000 distinct sequences, each sequence being 24 residues in length and consisting exclusively of glycine, serine, glutamate, and lysine. Though this set of sequences is relatively homogeneous in composition, we speculate our approach can be applied to disordered sequences of longer length and more heterogeneous composition, given the appropriate training set.
Cell adhesion molecules play subclass-specific roles in electrophysiological response and Schizophrenia risk
Authors: Li Xinzhe , Hu Hongru , Johansen Nelson , Quon Gerald
Published: November 2022

Multimodal assays such as Patch-seq that simultaneously profile molecular and cellular phenotypes of cells enable the identification of molecular underpinnings of electrophysiological response patterns in neurons. Here we analyzed Patch-seq measurements of thousands of mouse interneurons to identify subclass-specific genes associated with different electrophysiological features. We found extensive subclass specificity: even for the same ephys feature, largely unique sets of genes are associated with that feature in different subclasses. Well established ephys genes such as Reln demonstrated subclass specificity that was previously not reported. Surprisingly, we found that ion channels explained significantly less variation in ephys response across interneurons compared to other genes; in particular, gene sets enriched in cell adhesion genes were amongst the most associated. We found our gene sets associated with action potential dV/dt measurements explained significant heritability of Schizophrenia risk, suggesting a novel role of single neuron electrophysiology in Schizophrenia risk. Finally, we observed significant ephys function switching of cell adhesion molecules across subclasses; the same adhesion molecule was observed to associate with different functional ephys measurements in distinct subclasses and co-express with different genes, suggesting re-purposing of adhesion molecules in different subclasses. Overall, our results yield novel insight into the specificity of roles that individual genes and adhesion molecules play in both single neuron ephys response and Schizophrenia risk.
Clustered Cases of Human Adenovirus types 4, 7 and 14 Infections during the 2018 - 2019 Season revealed by US Department of Defense Respiratory Pathogen Surveillance and Whole Genome Sequencing
Authors: Pollio Adam R. , Fries Anthony C. , Yang Yu , Hughes Jerry J. , Fung Christian K. , Conte Matthew A. , Kuschner Robert A. , Collins Natalie D. , Macias Elizabeth A. , Hang Jun
Published: November 2022

Human adenoviruses (HAdV) are genetically diverse and can infect a number of tissues with severities varied from mild to fatal. HAdV types 3, 4, 7, 11, 14, 21 and 55 were associated with acute respiratory illnesses (ARI) outbreaks in the US and in other countries. The risk of outbreaks can be effectively controlled by HAdV vaccination or mitigated by screening and preventive measures. During the influenza season 2018 – 2019, the DoD Global Respiratory Pathogen Surveillance Program (DoDGRS) received 24,300 specimens. HAdV samples that produced positive cytopathic effects in viral cultivation were subjected to next-generation sequencing for genome sequence assembly, genome typing, whole genome phylogeny, and sequence comparative analyses. Variety of HAdV types were identified in this study, including HAdV types 1 – 7, 14, 55 and 56. HAdV types 4, 7 and 14 were found in clustered cases in Colorado, Florida, New York, and South Carolina. Comparative sequence analyses of these isolates revealed the emergence of novel genetic mutations despite the stability of adenovirus genomes. Genomic surveillance of HAdV related to possible outbreaks, shed light on prevalence, genetic divergence, and viral evolution of human adenoviruses. Continued surveillance will inform risk assessment and countermeasures.
Using large-scale whole-genome sequence data for single-step genomic predictions in maternal and terminal pig lines
Authors: Jang Sungbong , Ros-Freixedes Roger , Hickey John M. , Chen Ching-Yi , Herring William O. , Misztal Ignacy , Lourenco Daniela
Published: November 2022

Background

Whole-genome sequence (WGS) data harbor causative variants that may not be present in the regular SNP chip data. The objective of this study was to investigate the impact of using preselected variants from WGS for single-step genomic predictions in maternal and terminal pig lines with up to 1.8k sequenced and 104k imputed sequenced animals per line.

Methods

Two maternal and four terminal lines were investigated for eight and seven traits, respectively. The number of sequenced animals ranged from 1,365 to 1,491 in maternal lines and 381 to 1,865 in terminal lines. Imputation occurred within each line, and the number of animals imputed to sequence ranged from 66k to 76k in maternal lines and 29k to 104k in terminal lines. Two preselected SNP sets were generated based on genome-wide association study (GWAS). Top40k included the SNP with the lowest p-value in each of 40k genomic windows; ChipPlusSign included significant variants integrated into the regular porcine SNP chip. Single-step genomic predictions with equal or different SNP variances using those SNP sets were compared to the regular porcine SNP chip.

Results

In maternal lines, ChipPlusSign, and Top40k showed, on average, 0.62%, and 4.9% increased accuracy compared to the regular porcine SNP chip. The greatest changes were for fertility traits with Top40k, where the initial accuracy based on the SNP chip was low. However, for terminal lines, Top40k resulted in a loss of accuracy of 1% on average. Only ChipPlusSign provided a positive, albeit small, gain (0.85%). Assigning different variances for SNP slightly improved accuracies when using variances obtained from BayesR; however, the increase was inconsistent across the lines and traits.

Conclusions

The benefit of using sequence data depends on the line, size of the genotyped population, and how the WGS variants are preselected. When WGS is available on hundreds of thousands of animals, the advantage of sequence data is present but limited in maternal and terminal pig lines.
Epidemic control using stochastic and deterministic transmission models: performance comparison with and without parameter uncertainties
Authors: Flaig Julien , Houy Nicolas
Published: November 2022

Background

The spread of infectious diseases can be modeled using deterministic models assuming a continuous population or stochastic models assuming a discrete population. A stochastic model can be approximated by its deterministic counterpart under some conditions, however deterministic models are unable to captures effects pertaining to the discrete nature of populations, for instance epidemic extinction. We look into the choice of a model – deterministic or stochastic – from the perspective of decision making. We are interested in the influence of parameter uncertainties and of the quality of the estimates used to inform decisions.

Method

We consider an emerging disease in a closed population whose spread can be modeled by a stochastic SIR model or its deterministic version. Our objective is to minimize the cumulative number of symptomatic infected-days over the course of the epidemic by picking a vaccination policy out of three available options. We consider four decision making scenarios: based on the stochastic model or the deterministic model, and informed or under parameter uncertainty. We also consider different sample sizes covering parameter draws, stochastic model runs, or both depending on the scenario. We estimate the average performance of decision making in each scenario and for each sample size.

Results

The model used for decision making has an influence on the picked policies. The best achievable performance is obtained with the stochastic model, knowing parameter values, and for a large sample size. For small sample sizes, the deterministic model can outperform the stochastic model due to stochastic effects, both in the informed and the uninformed cases. Starting with the deterministic model under uncertainty, resolving uncertainties brings more benefit than switching to the stochastic model in our example.

Conclusion

This article illustrates the interplay between the choice of a type of model, parameter uncertainties, and sample sizes. It points to issues to be carefully considered when attempting to optimize a stochastic model.
Covid-19 in Brazil: A Cross-Sectional Immuno-Epidemical and Genomic Evaluation in a Pre-Omicron Era
Authors: de Oliveira Rodrigues Sarah , de Oliveira Gabriel Ferrari , e Silva Marcella Pâmela Costa , Pagnossa Jorge Pamplona
Published: November 2022

The seventh human coronavirus, was discovered and reported primarily in Wuhan, China. After intense seasons with repercussions in all areas ofhumanity, the pandemic demonstrates a new perspective. In Brazil, the pandemic concept has had impacts in vast areas, including mainly hospitals. This present study aims to describe, present and synthesize data that correlate the symptoms of passive and/or active patients for Covid-19 and their respective results of igg/igm serological tests in hospitals in cruzeiro, São Paulo. The form had been applied to 333 people and obtained conclusive results and several symptoms presented, in addition, asymptomatic cases were also analyzed and directed in the genomic study of variants of concern, as well as vaccination data in the study region.
Trait salivary alpha-amylase activity levels define the conditions for facilitation by L-DOPA of extinction consolidation
Authors: Andres E. , Chuan-Peng H. , Gerlicher A.M.V. , Meyer B. , Tüscher O. , Kalisch R.
Published: November 2022

Even after successful extinction, conditioned fear can return. Strengthening the consolidation of the fear-inhibitory safety memory formed during extinction is one way to counteract return of fear. In this preregistered direct replication study in male participants, we confirm that spontaneous post-extinction reactivations of a neural activation pattern evoked in the ventromedial prefrontal cortex (vmPFC) during extinction predict extinction memory retrieval 24 h later. We do not confirm that L-DOPA administration after extinction enhances retrieval and that this is mediated by enhancement of the number of vmPFC reactivations. However, additional non-preregistered analyses reveal a beneficial effect of L-DOPA on extinction retrieval when controlling for the trait-like stable baseline levels of salivary alpha-amylase enzymatic activity (trait sAA) levels that participants show on the three experimental days. Further, trait sAA negatively predicts retrieval, and this effect is rescued by L-DOPA treatment. Our results suggest that individuals with high basal levels of sympathetic nervous system (SNS) activity may have poor extinction and that L-DOPA may be selectively beneficial for these individuals, which holds potential for clinical applications.
Supremacy of attention based convolution neural network in classification of oral cancer using histopathological images
Authors: Singha Deo Bhaswati , Pal Mayukha , Panigrahi Prasanta K. , Pradhan Asima
Published: November 2022

Introduction

Oral cancer has grown to be one of the most prevalent malignant tumours and one of the deadliest diseases in emerging and low-to-middle income nations. The mortality rate can be significantly reduced if oral cancer is detected early and treated effectively.

Objectives

This study proposes an effective histopathological image classification model for oral cancer diagnosis using Vision Transformer deep learning based on multi-head attention mechanism.

Methods

The oral histopathological image dataset used in the study consists of 4946 images, which were categorized into 2435 images of healthy oral mucosa and 2511 images of oral squamous cell carcinoma (OSCC). In our proposed approach, along with Vision Transformer model eight pre-trained deep learning models known as Xception, Resnet50, InceptionV3, InceptionResnetV2, Densenet121, Densenet169, Densenet201 and EfficientNetB7 have been used for the comparative analysis. 90% of the images are used for training the models while the rest 10% of the images are used for testing purposes.

Results

Vision Transformer model achieved the highest classification accuracy of 97.78% in comparison to other considered deep learning models. Specificity, sensitivity and ROC AUC score are recorded as 96.88%, 98.74% and 97.74% respectively.

Conclusion

We found that our proposed Vision Transformer model outperforms compared to other pre-trained deep learning models, demonstrating a stronger transfer ability of the learning in histopathological image classification from the analysis of the obtained results. This method considerably lowers the cost of diagnostic testing while increasing the diagnostic effectiveness, and accuracy for oral cancer detection in patients of diverse origin.
Time-Aligned Hourglass Gastrulation Models in Rabbit and Mouse
Authors: Mayshar Y , Raz O , Cheng S , Ben-Yair R , Hadas R , Reines N , Mittnenzweig M , Ben-Kiki O , Lifshitz A , Tanay A , Stelzer Y
Published: November 2022

The hourglass model describes the convergence of species within the same phylum to a similar body plan during development, yet the molecular mechanisms underlying this phenomenon in mammals remain poorly described. Here, we compare rabbit and mouse time-resolved differentiation trajectories to revisit this model at single cell resolution. We modeled gastrulation dynamics using hundreds of embryos sampled between gestation days 6.0-8.5, and compare the species using a new framework for time-resolved single-cell differentiation-flows analysis. We find convergence toward similar cell state compositions at E7.5, underlied by quantitatively conserved expression of 76 transcription factors, despite divergence in surrounding trophoblast and hypoblast signaling. However, we observed noticeable changes in specification timing of some lineages, and divergence of primordial germ cells programs, which in the rabbit do not activate mesoderm genes. Comparative analysis of temporal differentiation models provides a new basis for studying the evolution of gastrulation dynamics across mammals.
A decision aid for policymakers to estimate the impact of e-cigarette flavour restrictions on population smoking and e-cigarette use prevalence among youth versus smoking prevalence among adults
Authors: Gibson Mark J , Munafò Marcus R , Attwood Angela S. , Dockrell Martin J. , Havill Michelle A. , Khouja Jasmine N
Published: November 2022

Background

Policy decisions should be evidence-based, but the magnitude of intended and unintended impacts cannot always be easily estimated from the available data. For example, banning flavours in electronic cigarettes (e-cigarettes) to reduce appeal to non-smoking young people could have the intended impact by reducing youth vaping but could have negative consequences for adult smokers and vapers.

Methods

We developed a decision aid to help policymakers make informed decisions on the potential net impact of a ban on e-cigarette flavours. We estimated the number of non-smoking youth who would be deterred from ever vaping and subsequently ever smoking, and the number of smokers and ex-smokers who would be deterred from quitting or encouraged to relapse, to determine whether the benefits to youth outweigh the costs to existing smokers and vapers. This aid then outputs a report with the results graphically depicted to aid interpretability.

Results

We demonstrated the value of this decision aid using data from various sources to estimate the impact of a flavour ban in three populations: the general UK population, low-socioeconomic position UK population, and the general US population. All three examples suggested a negative net population impact of a ban. These reports were then presented to the all-party parliamentary group for vaping.

Conclusions

We demonstrate how decision aids can be used to help policymakers arrive at evidence-based decisions efficiently and can be used to quickly obtain up-to-date estimates as new data becomes available.
Factors influencing the use of multiple HIV prevention services among Transport workers in a City in Southwestern Uganda
Authors: Betunga Benjamin , Atuhaire Phionah , Nakasiita Catherine , Kanyamuneza Christa , Namiiro Proscovia , Tugume Joseph , Hairat Matovu , Sarki Ahmed M , Mugabi Benedicto , Lilian Birungi , Mugisha Richard , Kumakech Edward , Asiimwe John Baptist
Published: November 2022

Introduction

Over the last three decades, there has been tremendous progress in curbing the HIV epidemic in Uganda, although the HIV prevalence remains high among transport workers. Using multiple HIV prevention services has been found to decrease the risk of acquiring HIV when tailored to individuals at risk of HIV exposure, including transport workers. Therefore, we assessed the uptake of multiple HIV prevention services (≥2) and associated factors among transport workers in a city in Southwestern Uganda.

Methods

A cross-sectional study was conducted between November 2021 and February 2022. Transport workers comprising motorcycle taxi riders, and motor vehicle and truck drivers, aged 18 to 55 years were selected and responded to an interviewer-administered questionnaire. We conducted descriptive statistical and logistic regression analysis to identify independent factors associated with the uptake of multiple HIV prevention services.

Results

Out of 420 participants, 97.6% were male, with a median age of 28 years and the majority were aged <34 years (84.6%). Overall, less than half (45.3%) of the participants had used multiple (≥2) HIV prevention services within a one-year period. Most of the participants had used condoms (32.2%) followed by voluntary HIV counseling and testing (27.1%), and safe male circumcision (17.3%). Most participants who tested for HIV had ever used condoms (16.2%), followed by those who received safe male circumcision and had ever used condoms (15%), and those who tested for HIV and had started on antiretroviral therapy (ART) (9.1%). In the adjusted model, factors that were significantly associated with the use of multiple HIV prevention services included religion (AOR=2.69, 95% CI=1.38-5.23), the number of concurrent sexual partners (AOR=2.52, 95% CI=1.45-4.37), prior HIV testing and awareness of HIV serostatus (AOR=0.23, 95% CI=0.13-0.41), awareness of HIV prevention services (AOR=5.45, 95% CI=1.82-16.33), and financial payment to access HIV services (AOR=4.80, 95% CI=2.33-9.88).

Conclusions

The uptake of multiple HIV prevention services among transport workers remains suboptimal. This study suggests that individual behavioral factors influence the use of multiple HIV services compared with other factors. Therefore, differentiated strategies are needed to increase the utilization of HIV prevention services to curb the new HIV infections among transport workers.
Evaluating the effectiveness of mindfulness alone compared to exercise and mindfulness on fatigue in women with gynaecology cancer (GEMS): Protocol for a randomised feasibility trial
Authors: McCloy Kairen , Hughes Ciara , Dunwoody Lynn , Marley Joanne , Cleland Ian , Cruciani Federico , Saunders Catherine , Gracey Jackie
Published: November 2022

Background

In 2020 Globocan reported nearly 1.4 million new cases of gynaecology cancer worldwide. Cancer related fatigue has been identified as a symptom that can be present for gynaecology cancer patients many years after treatment. The current evidence around the management of this symptom suggests that exercise has the most positive outcome. However, some ambiguity remains around the evidence and whether it can address all areas of fatigue effectively. More recently, other interventions such as mindfulness have begun to show a favourable response to the management of symptoms for cancer patients. To date there has been little research that explores the feasibility of using both these interventions together in a gynaecology cancer population. This study aims to explore the feasibility of delivering an intervention that involves mindfulness and mindfulness and exercise and will explore the effect of this on fatigue, sleep, mood and quality of life.

Methods/Design

This randomised control trial will assess the interventions outcomes using a pre and post design and will also include a qualitative process evaluation. Participants will be randomised into one of 2 groups. One group will undertake mindfulness only and the other group will complete exercise and mindfulness. Both groups will use a mobile application to complete these interventions over 8 weeks. The mobile app will be tailored to reflect the group the participants have drawn during randomisation. Self-reported questionnaire data will be assessed at baseline prior to commencing intervention and at post intervention. Feasibility will be assessed through recruitment, adherence, retention and attrition. Acceptability and participant perspective of participation (process evaluation), will be explored using focus groups.

Discussion

This trial will hope to evidence and demonstrate that combination of two interventions such as mindfulness and exercise will further improve outcomes of fatigue and wellbeing in gynaecology cancer. The results of this study will be used to assess (i) the feasibility to deliver this type of intervention to this population of cancer patients using a digital platform; (ii) assist this group of women diagnosed with cancer to manage fatigue and other symptoms of sleep, mood and impact their quality of life.

Trial registration

NCT05561413
Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: A systematic review and meta-regression analysis
Authors: Stannah James , Soni Nirali , Lam Jin Keng Stephen , Giguère Katia , Mitchell Kate M , Kronfli Nadine , Larmarange Joseph , Moh Raoul , Nouaman Marcelin N’zebo , Kouamé Gérard Menan , Maheu-Giroux Mathieu , Boily Marie-Claude
Published: November 2022

Background

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment including socio-economic disadvantages, stigma, and criminalization that increase their vulnerability to HIV acquisition and transmission and undermine progress towards ending AIDS. This systematic review explores progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa.

Methods

We searched Embase, Medline, Global Health, Scopus, and Web of Science from January 1980-March 2022 for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and/or HIV incidence among MSM in Africa. We pooled surveys using Bayesian generalized linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men.

Findings

Of 8,992 articles identified, we included 148 unique studies published from 2005-2022. HIV testing increased over time in Central/Western and Eastern Africa and in 2020, we estimate that 88% (95% credible interval (CrI) 57-97%) of MSM had tested in the past 12 months, but 66% (19-94%) of MSM living with HIV knew their HIV status, although this is probably underestimated given non-disclosure. Current ART use increased over time in Central/Western (ORyear=1.4, 95%CrI 1.1-2.0, N=8) and Eastern/Southern Africa (ORyear=1.4, 1.0-1.8, N=17) and in 2020 we estimate that 75% (18-98%) of MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence viral suppression increased, and in 2020 we estimate that only 62% (12-95%) of MSM living with HIV were virally suppressed. HIV incidence among MSM did not decrease over time (IRRyear=1.0, 0.7-1.3, N=38) and remained high in 2020 (5.4 per 100 person-years, 0.9-33.9) and substantially higher (27-150 times higher) than among all men.

Interpretation

No decreases in HIV incidence have been observed among MSM in Africa over time, despite some increases in HIV testing and ART use. Achieving the UNAIDS 95-95-95 targets for diagnosis, treatment, and viral suppression equitably for all requires renewed focus on this key population. Combination interventions for MSM are urgently required to reduce disparities in HIV incidence and tackle the social, structural, and behavioural factors that make MSM vulnerable to HIV acquisition.

Funding

US National Institutes of Health, UK Medical Research Council, Canadian Institutes of Health Research, Fonds de Recherche du Québec – Santé.
Enhancing the performance of Magnets photosensors through directed evolution
Authors: Baumschlager Armin , Weber Yanik , Cánovas David , Dionisi Sara , Khammash Mustafa
Published: November 2022

Photosensory protein domains are the basis of optogenetic protein engineering. These domains originate from natural sources where they fulfill specific functions ranging from the protection against photooxidative damage to circadian rhythms. When used in synthetic biology, the features of these photosensory domains can be specifically tailored towards the application of interest, enabling their full exploitation for optogenetic regulation in basic research and applied bioengineering. In this work, we develop and apply a simple, yet powerful, directed evolution and high-throughput screening strategy that allows us to alter the most fundamental property of the widely used nMag/pMag photodimerization system: its light sensitivity. We identify a set of mutations located within the photosensory domains, which either increase or decrease the light sensitivity at sub-saturating light intensities, while also improving the dark-to-light fold change in certain variants. For some of these variants, photosensitivity and expression levels could be changed independently, showing that the shape of the light-activity dose-response curve can be tuned and adjusted. We functionally characterize the variantsin vivoin bacteria on the single-cell and the population levels. We further show that a subset of these variants can be transferred into the mOptoT7 for gene expression regulation in mammalian cells. We demonstrate increased gene expression levels for low light intensities, resulting in reduced potential phototoxicity in long-term experiments. Our findings expand the applicability of the widely used Magnets photosensors by enabling a tuning towards the needs of specific optogenetic regulation strategies. More generally, our approach will aid optogenetic approaches by making the adaptation of photosensor properties possible to better suit specific experimental or bioprocess needs.
Timing of integration into the chromosome is critical for the fitness of an integrative and conjugative element and its bacterial host
Authors: McKeithen-Mead Saria A. , Grossman Alan D.
Published: November 2022

Integrative and conjugative elements (ICEs) are major contributors to genome plasticity in bacteria. ICEs reside integrated in the chromosome of a host bacterium and are passively propagated during chromosome replication and cell division. When activated, ICEs excise from the chromosome and may be transferred through the ICE-encoded conjugation machinery into a recipient cell. Integration into the chromosome of the new host generates a stable transconjugant. Although integration into the chromosome of a new host is critical for the stable acquisition of ICEs, few studies have directly investigated the molecular events that occur in recipient cells during generation of a stable transconjugant. We found that integration of ICEBs1, an ICE ofBacillus subtilis, occurred several generations after initial transfer to a new host. Premature integration in new hosts led to cell death and hence decreased fitness of the ICE and transconjugants. Host lethality due to premature integration was caused by rolling circle replication that initiated in the integrated ICEBs1and extended into the host chromosome, resulting in catastrophic genome instability. Our results demonstrate that the timing of integration of an ICE is linked to cessation of autonomous replication of the ICE, and that perturbing this linkage leads to a decrease in ICE and host fitness due to a loss of viability of transconjugants. Linking integration to cessation of autonomous replication appears to be a conserved regulatory scheme for mobile genetic elements that both replicate and integrate into the chromosome of their host.

Author Summary

Horizontal gene transfer helps drive microbial evolution, enabling bacteria to rapidly acquire new genes and traits. Integrative and conjugative elements (ICEs) are mobile genetic elements that reside integrated in the chromosome of a host bacterium and can transfer to other cells via a contact-dependent mechanism called conjugation. Some ICEs contain genes that confer important traits to their bacterial hosts, including antibiotic resistances, metabolic capabilities, and pathogenicity. Central to the propagation of ICEs and other mobile genetic elements is the balance between dissemination to new hosts and maintenance within a host, while minimizing the fitness burden imposed on their hosts. We describe an underlying regulatory mechanism that allows for an ICE that has entered into a nascent host to replicate and potentially spread to other hosts before integration into the chromosome. Integration occurs shortly after or concomitant with cessation of ICE replication. Disruption of this regulatory link results in premature integration and fitness defects for both the host and the ICE; lethality for the host and reduced spread of the ICE.
Septins and K63 chains form separate bacterial microdomains during autophagy of entrappedShigella
Authors: Lobato-Márquez Damián , Conesa José Javier , López-Jiménez Ana Teresa , Divine Michael E. , Pruneda Jonathan N. , Mostowy Serge
Published: November 2022

During host cell invasion,Shigellaescapes to the cytosol and polymerizes actin for cell-to-cell spread. To restrict cell-to-cell spread, host cells employ cell-autonomous immune responses including antibacterial autophagy and septin cage entrapment. How septins interact with autophagy to targetShigellato destruction is poorly understood. Here, we employed a correlative light and cryo-soft X-ray tomography (cryo-SXT) pipeline to studyShigellaseptin cage entrapment in its near native state. Quantitative cryo-SXT showed thatShigellafragments mitochondria and enabled visualization of X-ray dense structures (∼30 nm resolution) surroundingShigellaentrapped in septin cages. Using Airyscan confocal microscopy, we observed Lysine 63 (K63)-linked ubiquitin chains decorating septin caged entrappedShigella. Remarkably, septins and K63 chains form separate bacterial microdomains, indicating they are recruited separately during antibacterial autophagy. Cryo-SXT and live cell imaging revealed an interaction between septins and LC3B-positive membranes during autophagy ofShigella. Together, these findings demonstrate how septin cagedShigellaare targeted to autophagy and provide fundamental insights into autophagy-cytoskeleton interactions.
Stochastic differential equation modelling of cancer cell migration and tissue invasion
Authors: Katsaounis Dimitrios , Chaplain Mark A.J. , Sfakianakis Nikolaos
Published: November 2022

Invasion of the surrounding tissue is a key aspect of cancer growth and spread involving a coordinated effort between cell migration and matrix degradation, and has been the subject of mathematical modelling for almost 30 years. In this current paper we address a long-standing question in the field of cancer cell migration modelling. Namely, identify the migratory pattern and spread of individual cancer cells, or small clusters of cancer cells, when the macroscopic evolution of the cancer cell colony is dictated by a specific partial differential equation (PDE).

We show that the usual heuristic understanding of the diffusion and advection terms of the PDE being one-to-one responsible for the random and biased motion of the solitary cancer cells, respectively, is not precise. On the contrary, we show that the drift term of the correct stochastic differential equation (SDE) scheme that dictates the individual cancer cell migration, should account also for the divergence of the diffusion of the PDE. We support our claims with a number of numerical experiments and computational simulations.