bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

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

ABSTRACTThe 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

AbstractBackgroundPolicy 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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

AbstractIntroductionOver 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.MethodsA 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.ResultsOut 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).ConclusionsThe 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

AbstractBackgroundIn 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/DesignThis 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.DiscussionThis 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 registrationNCT05561413
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

ABSTRACTBackgroundGay, 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.MethodsWe 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.FindingsOf 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.InterpretationNo 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.FundingUS 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

AbstractPhotosensory 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

AbstractIntegrative 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 SummaryHorizontal 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

AbstractDuring 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

AbstractInvasion 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.
Multi-omic spatial profiling reveals the unique virus-driven immune landscape of COVID-19 placentitis
Authors: Pugh Matthew , Fennell Éanna , Leahy Ciara I , Perry Tracey , Hargitai Beata , Marton Tamas , Hunter Kelly J. , Halford Graham , Yilmaz Hale Onder , Stamataki Zania , Reynolds Gary , Hill Harriet J. , Willcox Benjamin E. , Steven Neil , Thornton Catherine A. , Dojcinov Stefan D. , Culhane Aedin , Murray Paul G. , Taylor Graham S. 
Published: November 2022

SummaryCOVID-19 placentitis, a rare complication of maternal SARS-CoV-2 infection, only shows detectable virus in the placenta of a subset of cases. We provide a deep multi-omic spatial characterisation of placentitis from obstetrically complicated maternal COVID-19 infection. We found that SARS-CoV-2 infected placentas have a distinct transcriptional and immunopathological signature. This signature overlaps with virus-negative cases supporting a common viral aetiology. An inverse correlation between viral load and disease duration suggests viral clearance over time. Quantitative spatial analyses revealed a unique microenvironment surrounding virus-infected trophoblasts characterised by PDL1-expressing macrophages, T-cell exclusion, and interferon blunting. In contrast to uninfected mothers, ACE2 was localised to the maternal side of the placental trophoblast layer of almost all mothers with placental SARS-CoV-2 infection, which may explain variable susceptibility to placental infection. Our results demonstrate a pivotal role for direct placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis.Graphical Abstract