bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutually exclusive spectral biclustering and its applications in cancer subtyping
Authors: Liu Fengrong , Yang Yaning , Xu Xu Steven , Yuan Min 
Published: May 2022

AbstractMany soft biclustering algorithms have been developed and applied to various biological and biomedical data analyses. However, until now, few mutually exclusive (hard) biclustering algorithms have been proposed although they can be extremely useful for identify disease or molecular subtypes based on genomic or transcriptomic data. We considered the biclustering problem of expression matrices as a bipartite graph partitioning problem and developed a novel biclustering algorithm, MESBC, based on Dhillon’s spectral method to detect mutually exclusive biclusters. MESBC simultaneously detects relevant features (genes) and corresponding subgroups, and therefore automatically uses the signature features for each subtype to perform the clustering, improving the clustering performance. MESBC could accurately detect the pre-specified biclusters in simulations, and the identified biclusters were highly consistent with the true labels. Particularly, in setting with high noise, MESBC outperformed existing NMF and Dhillon’s method and provided markedly better accuracy. Analysis of two TCGA datasets (LUAD and BRAC cohorts) revealed that MESBC provided similar or more accurate prognostication (i.e., smaller p value) for overall survival in patients with breast and lung cancer, respectively, compared to the existing, gold-standard subtypes for breast (PAM50) and lung cancer (integrative clustering). In the TCGA lung cancer patients, MESBC detected two clinically relevant, rare subtypes that other biclustering or integrative clustering algorithms could not detect. These findings validated our hypothesis that MESBC could improve molecular subtyping in cancer patients and potentially facilitate better individual patient management, risk stratification, patient selection, therapeutic assignments, as well as better understanding gene signatures and molecular pathways for development of novel therapeutic agents.
An evolutionary perspective on the origin, conservation and binding partner acquisition of tankyrases
Authors: Sowa Sven T. , Bosetti Chiara , Galera-Prat Albert , Johnson Mark S. , Lehtiö Lari 
Published: May 2022

AbstractTankyrases are poly-ADP-ribosyltransferases that regulate many crucial and diverse cellular processes in humans such as Wnt signaling, telomere homeostasis, mitotic spindle formation and glucose metabolism. While tankyrases are present in most animals, functional differences across species exist. In this work we confirm the widespread distribution of tankyrases throughout the branches of multicellular animal life and identified the single-celled choanoflagellates as earliest origin of tankyrases. We further show that sequence and structural aspects of TNKSs are well conserved even between highly diverged species. We also experimentally characterized an anciently diverged tankyrase homolog from the sponge Amphimedon queenslandica and show that the basic functional aspects, such as poly-ADP-ribosylation activity and interaction with the canonical tankyrase binding peptide motif, are conserved. Conversely, the presence of tankyrase binding motifs in orthologs of confirmed interaction partners vary greatly between species, indicating that tankyrases have different sets of interaction partners depending on the animal lineage. Overall, our analysis suggests a remarkable degree of conservation for tankyrases, although their regulatory functions in cells have likely changed considerably throughout evolution.
Culture Associated DNA Methylation Changes Impact on Cellular Function of Human Intestinal Organoids
Authors: Edgar Rachel D , Perrone Francesca , Foster April R , Payne Felicity , Lewis Sophia , Nayak Komal M , Kraiczy Judith , Cenier Aurélie , Torrente Franco , Salvestrini Camilla , Heuschkel Robert , Hensel Kai O , Harris Rebecca , Jones D. Leanne , Zerbino Daniel R , Zilbauer Matthias 
Published: May 2022

ABSTRACTBackground & AimsHuman intestinal epithelial organoids (IEO) are a powerful tool to model major aspects of intestinal development, health and diseases, as patient derived cultures retain many features found in-vivo. A necessary aspect of the organoid model is the requirement to expand cultures in-vitro through several rounds of passaging. This is of concern, as the passaging of cells has been shown to affect cell morphology, ploidy, and function. In this study, we address concerns around long term passaging of IEO to better characterise and define effects on cell morphology and function.MethodsHere we have analysed 173 human IEO from two sampling sites, terminal ileum and sigmoid colon and examined the effect of culture duration on DNA methylation (DNAm), gene expression and cellular function including their response to proinflammatory cytokines and in-vitro cell differentiation.ResultsOur analyses revealed a major effect of culture duration on DNAm, leading to significant changes at 61,337 loci representing approximately 8% of all CpGs tested. Although global cellular functions such as gut segment-specific gene expression remained stable, a subset of methylation changes correlated with altered gene expression at baseline as well as in response to inflammatory cytokine exposure and in-vitro differentiation. Importantly, epigenetic changes were found to be enriched in genomic regions associated with colonic cancer and distant to the site of replication indicating similarities to malignant transformation.ConclusionsOur study reveals culture-associated epigenetic, transcriptomic and functional changes in human mucosa derived IEO and highlights the importance of considering passage number as a potentially confounding factor.SynopsisThis work describes cell culture induced changes to DNA methylation, gene expression and cellular function in human IEO. Globally organoids lost DNA methylation with time in culture while DNA methylation also became generally more variable. This work suggests a shifted epigenetic profile in organoids cultured long-term.
Molecular Aggregation Induced Photoacoustics for NIR-II in vivo Imaging
Authors: Chang Zong , Liu Liangjian , Liu Chenchen , Zhao Shubi , Chen Jiaqi , Zhang Wenxin , Wang Xiao , Liu Chengbo , Xie Xiaojiang , Sun Qinchao 
Published: May 2022

AbstractMolecular aggregation induced photo-properties alteration has been found to play a crucial role in the light induced processes, such as aggregation induced emission (AIE) and J aggregation induced dramatic absorption red shift. The light induced acoustic process (photoacoustic) is also considered to be one of the most essential characters of the light absorbing molecules. However, to the best of our knowledge, the molecular aggregation induced photoacoustic effect (MAIPA) has never been reported. Herein, we report the first MAIPA effect for which the PA intensity is dominated by the molecular aggregation, rather than by absorbance as usual concerned. Molecular aggregation induces a strong electronic coupling effect, resulting in significant absorption suppression from the individual state to highly aggregated state (around 5 molecules aggregated). However, the corresponding PA efficiency was found to be about 2-orders of magnitude greater for the latter. A well-behaved linear correlation between the molecular aggregation level and MAIPA effect was observed. The surprisingly significant MAIPA effect was realized via novel NIR-II squaraine-benzothiopyrylium dyes. Excellent photophysical properties of the novel NIR-II dyes were achieved, such as large absorption extinction coefficient and high photostability. Thanks to the relatively narrow FWHM and the high PA efficiency of SQN2@PMAOPEG and ZC825@BSA, in vivo multiplex PA imaging was demonstrated for tumor tissue and macrophage cells, blood and lymphoid vessels.
Highly efficient genome editing in barley using novel LbCas12a variants and impact of sgRNA architecture
Authors: Lawrenson Tom , Hinchliffe Alison , Forner Macarena , Harwood Wendy 
Published: May 2022

AbstractWe report the first successful, high efficiency use of LbCas12a in barley and describe the development and application of two novel Cas12a variants. In total we compared five coding sequence (CDS) variants including the two novel ones and two guide architectures over 5 different target genes using twenty different guides. We found large differences in editing efficiencies between the different CDS versions (0-87%) and guide architectures (0-70%) and show our two novel CDS versions massively outperform the others on test in this species. We show heritability of mutations generated. Our findings highlight the importance of optimising CRISPR systems for individual species and are likely to aid the use of LbCas12a in other monocot species.
Caregivers’ perception of risk for malaria, helminth infection and malaria-helminth co-infection among children living in urban and rural settings of Senegal: a qualitative study
Authors: Afolabi Muhammed O. , Sougou Ndèye Mareme , Diaw Aminata , Sow Doudou , Manga Isaac A. , Mbaye Ibrahima , Greenwood Brian , Ndiaye Jean Louis A. 
Published: May 2022

AbstractMalaria parasites and worms frequently co-exist in children living in low-and middle-income countries where existing vertical control programmes for the control of these two conditions are not operating at optimal levels. This gap necessitates the development and implementation of strategic interventions to achieve effective control and eventual elimination of these co-infections. Central to the successful implementation of any intervention is its acceptance and uptake by caregivers whose perception about the risk for malaria-helminth co-infection has been little documented. Therefore, we conducted a qualitative study to understand the caregivers’ perspectives about the risk as well as the behavioural and social risk factors promoting malaria-helminth co-infection among pre-school and school-aged children living in endemic rural and urban communities in Senegal. In June and December 2021, we conducted individual and group interviews, and participant observations, among 100 primary caregivers of children recruited from villages in southeast Senegal and among leaders and teachers of Koranic schools in western Senegal. Our findings showed that a majority of the study participants in the two settings demonstrated a high level of perception of risk for malaria and acceptable awareness about handwashing practices, but had misconceptions that malaria-helminth co-infection was due to a combination of excessive consumption of sugary food and mosquito bites. Our observations revealed many factors in the house structures, toilet practices and handwashing with ashes and sands, which the caregivers did not consider as risks for malaria-helminth co-infections. These findings underscore the need to promote caregivers’ awareness about the existence and risk of malaria-helminth co-infection in children. This approach would assist in addressing the caregivers’ misconceptions about the occurrence of the co-infection and could enhance their uptake of the strategic interventions targeted at achieving control and subsequent elimination of malaria and helminth co-infection.
Assessment of oxidative stress markers in elderly patients with SARS-CoV-2 infection and potential prognostic implications. An observational study
Authors: Vazquez-Agra Nestor , Marques-Afonso Ana-Teresa , Cruces-Sande Anton , Novo-Veleiro Ignacio , Pose-Reino Antonio , Mendez-Alvarez Estefania , Soto-Otero Ramon , Hermida-Ameijeiras Alvaro 
Published: May 2022

AbstractThe aim of the study was to evaluate the correlation of plasma levels of thiobarbituric acid reactive substances (TBARS) and reduced thiols with morbidity, mortality and immune response in SARS-CoV-2 infection. This was an observational study that included inpatients with SARS-CoV-2 infection greater than 65 years old. Individuals were followed up until 12 months after hospital discharge. Demographic, clinical and laboratory variables were collected. Plasma levels of TBARS and reduced thiols were quantified as a measure of lipid and protein oxidation, respectively. Events of interest (fatal and non-fatal) were quantified at hospital discharge, third, sixth and twelfth-month post-discharge. The outcomes were differences in oxidative stress markers between groups of interest and time to a negative RT-qPCR and to significant anti-SARS-CoV-2 IgM titers. There were 61 patients (57% women) with a mean age of 83 years old. Patients with higher levels of TBARS and lower levels of reduced thiols had more risk of fatal and non-fatal events between admission and the first 12 months post-discharge. The presence of any event (fatal or non-fatal) at the end of the first 12 months post-discharge was correlated with TBARS levels, anti-SARS-CoV-2 IgM titers, lactate dehydrogenase, platelet count and neutrophil and lymphocyte count. We found a correlation between plasma reduced thiols and time to achieve significant anti-SARS-CoV-2 IgM titers. Assessment of some parameters related to oxidative stress could help to identify groups of patients with a higher risk of morbidity and mortality during and after SARS-CoV-2 infection.
Adherence Monitoring Methods to Measure Virological Failure in People Living with HIV on Long-Term Antiretroviral Therapy in Uganda
Authors: Okoboi Stephen , Musaazi Joseph , King Rachel , Lippman Sheri A. , Kambugu Andrew , Mujugira Andrew , Izudi Jonathan , Parkes-Ratanshi Rosalind , Kiragga Agnes N. , Castelnuovo Barbara 
Published: May 2022

AbstractAppointment keeping and self-report within 7-day or and 30-days recall periods are non-objective measures of antiretroviral treatment (ART) adherence. We assessed incidence of virological failure (VF), predictive performance and associations of these adherence measures with VF among adults on long-term ART. Data for persons initiated on ART between April 2004 and April 2005, enrolled in a long-term ART cohort at 10-years on ART (baseline) and followed until December 2021 was analyzed. VF was defined as two consecutives viral loads ≥1000 copies/ml at least within 3-months after enhanced adherence counselling. We estimated VF incidence using Kaplan-Meier and Cox-proportional hazards regression for associations between each adherence measure (analyzed as time-dependent annual values) and VF. The predictive performance of appointment keeping and self-reporting for identifying VF was assessed using receiver operating characteristic curves and reported as area under the curve (AUC). We included 900 of 1,000 participants without VF at baseline: median age was 47 years (Interquartile range: 41-51), 60% were women and 88% were virally suppressed. ART adherence was ≥95% for all three adherence measures. Twenty-one VF cases were observed with an incidence rate of 4.37 per 1000 person-years and incidence risk of 2.4% (95% CI: 1.6%-3.7%) over the 5-years of follow-up. Only 30-day self-report measure was associated with lower risk of VF, adjusted hazard ratio (aHR)=0.14, 95% CI:0.05–0.37). Baseline CD4 count ≥200cells/ml was associated with lower VF for all adherence measures. The 30-day self-report measure demonstrated the highest predictive performance for VF (AUC=0.751) compared to appointment keeping (AUC=0.674), and 7-day self-report (AUC=0.687). The incidence of virological failure in this study cohort was low. Whilst 30-day self-report was predictive, appointment keeping and 7-day self-reported adherence measures had low predictive performance in identifying VF. Viral load monitoring remains the gold standard for adherence monitoring and confirming HIV treatment response.
Human Mobility and Infection from Covid-19 in the Osaka Metropolitan Area
Authors: Kato Haruka , Takizawa Atsushi 
Published: May 2022

AbstractControlling human mobility is thought to be an effective measure to prevent the spread of the COVID-19 pandemic. This study aims to clarify the human mobility types that impacted the number of COVID-19 cases during the medium-term COVID-19 pandemic in the Osaka metropolitan area. The method used in this study was analysis of the statistical relationship between human mobility changes and the total number of COVID-19 cases after two weeks. In conclusion, the results indicate that it is essential to control the human mobility of groceries/pharmacies to less than 0% and that of parks to more than -20%. The most significant finding for urban sustainability is that urban transit was not found to be a source of infection. Hence governments in cities around the world may be able to encourage communities to return to transit mobility, if they are able to follow the kind of hygiene processes conducted in Osaka.
Beneficial influence of single-stage posterior surgery for the treatment of lumbar brucella spondylitis combined with spondylolisthesis
Authors: Zhang Yao , Zhao Chang-song , Chen Jia-min , Zhang Qiang 
Published: May 2022

AbstractWe aimed to evaluate the clinical efficacy of the single-stage posterior surgical treatment for patients of lumbar brucella spondylitis combined with spondylolisthesis. In this study, we performed a retrospective analysis of 16 patients with lumbar brucellosis spondylitis combined with spondylolisthesis from January 2015 to January 2019. All patients underwent single-stage posterior lumbar debridement, reduction, interbody fusion, and instrumentation. Preoperative and postoperative of the visual analog scale (VAS), the Japanese orthopedic association scores (JOA), the Oswestry disability index (ODI), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were compared. In addition, the spondylolisthesis reduction rate, reduction loss rate, interbody fusion rate, and complication rate were recorded. VAS, JOA, ODI, ESR, and CRP were conducted with repeated analysis of variance data at different follow-ups. The postoperative follow-up was 12 to 36 months, with an average of (25.0±8.1) months. VAS, JOA, ODI, ESR, and CRP were significantly better at two-week and one-year follow-up than preoperative results (P=0.000, respectively). In addition, one year after the operation, VAS, JOA, ODI, ESR, and CRP showed a significant improvement (P=0.000, respectively). The average spondylolisthesis reduction in two weeks after operation was (91.2±6.7) %, and the median reduction loss rate in one year after operation was 8.0 (5.0,9.8) %. At the last follow-up, all patients achieved interbody fusion, no loosening and fracture of instrumentation were found, and no recurrence happened. Single-stage posterior operation for lumbar debridement, reduction, interbody fusion, and instrumentation is beneficial for treating lumbar brucellosis spondylitis combined with spondylolisthesis. Furthermore, the reconstruction of spinal stability may relieve pain, heal lesions, and improve patients’ living.
Modeling ecological communities when composition is manipulated experimentally
Authors: Skwara Abigail , Lemos-Costa Paula , Miller Zachary R. , Allesina Stefano 
Published: May 2022

AbstractIn an experimental setting, the composition of ecological communities can be manipulated directly. Starting from a pool of n species, one can co-culture species in different combinations, spanning mono-cultures, pairs of species, and all the way up to the full pool. Here we advance methods aimed at inferring species interactions from data sets reporting the density attained by species in a variety of sub-communities formed from the same pool.First, we introduce a fast and robust algorithm to estimate parameters for simple statistical models describing these data, which can be combined with likelihood maximization approaches. Second, we derive from consumer-resource dynamics statistical models with few parameters, which can be applied to study systems where only a small fraction of the potential sub-communities have been observed. Third, we show how a Weighted Least Squares (WLS) framework can be used to account for the fact that species abundances often display a strong relationship between means and variances.To illustrate our approach, we analyze data sets spanning plants, bacteria, phytoplankton, as well as simulations, recovering a good fit to the data and demonstrating the ability to predict experiments out-of-sample.We greatly extend the applicability of recently proposed methods, opening the door for the analysis of larger pools of species.
Computationally efficient mechanism discovery for cell invasion with uncertainty quantification
Authors: VandenHeuvel Daniel J. , Drovandi Christopher , Simpson Matthew J. 
Published: May 2022

AbstractParameter estimation for mathematical models of biological processes is often difficult and depends significantly on the quality and quantity of available data. We introduce an efficient frame-work using Gaussian processes to discover mechanisms underlying delay, migration, and proliferation in a cell invasion experiment. Gaussian processes are leveraged with bootstrapping to provide uncertainty quantification for the mechanisms that drive the invasion process. Our frame-work is efficient, parallelisable, and can be applied to other biological problems. We illustrate our methods using a canonical scratch assay experiment, demonstrating how simply we can explore different functional forms and develop and test hypotheses about underlying mechanisms, such as whether delay is present. All code and data to reproduce this work are available athttps://github.com/DanielVandH/EquationLearning.jl.1Author summaryIn this work we introduce uncertainty quantification into equation learning methods, such as physics-informed and biologically-informed neural networks. Our framework is computationally efficient and applicable to problems with unknown nonlinear mechanisms that we wish to learn from experiments where only sparse noisy data are available. We demonstrate our methods on a canonical scratch assay experiment from cell biology and show the underlying mechanisms can be learned, providing confidence intervals for functional forms and for solutions to partial differential equation models believed to describe the experiment.
Haploidy-linked cell proliferation defects limit larval growth in Zebrafish
Authors: Yaguchi Kan , Saito Daiki , Menon Triveni , Matsura Akira , Hosono Miyu , Mizutani Takeomi , Kotani Tomoya , Nair Sreelaja , Uehara Ryota 
Published: May 2022

AbstractHaploid larvae in non-mammalian vertebrates are lethal with characteristic organ growth retardation collectively called “haploid syndrome.” In contrast to mammals whose haploid intolerance is attributed to imprinting misregulation, the cellular principle of haploidy-linked defects in non-mammalian vertebrates remains unknown. Here, we investigated cellular defects that disrupt the ontogeny of gynogenetic haploid zebrafish larvae. Unlike diploid control, haploid larvae manifested unscheduled cell death at the organogenesis stage, attributed to haploidy-linked p53 upregulation. Moreover, we found that haploid larvae specifically suffered the gradual aggravation of mitotic spindle monopolarization during 1-3 days post fertilization, causing spindle assembly checkpoint-mediated mitotic arrest throughout the entire body. High-resolution imaging revealed that this mitotic defect accompanied the haploidy-linked centrosome loss occurring concomitantly with the gradual decrease in larval cell size. Either resolution of mitotic arrest or depletion of p53 partially improved organ growth in haploid larvae. Based on these results, we propose that haploidy-linked mitotic defects and cell death are parts of critical cellular causes shared among vertebrates that limit the larval growth in the haploid state, contributing to an evolutionary constraint on allowable ploidy status in the vertebrate life cycle.