bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human colorectal pre-cancer atlas identifies distinct molecular programs underlying two major subclasses of pre-malignant tumors
Authors: Chen Bob , McKinley Eliot T. , Simmons Alan J. , Ramirez-Solano Marisol A. , Zhu Xiangzhu , Southard-Smith Austin N. , Markham Nicholas O. , Sheng Quanhu , Drewes Julia L. , Xu Yanwen , Heiser Cody N. , Zhou Yuan , Revetta Frank , Berry Lynne , Zheng Wei , Washington M. Kay , Cai Qiuyin , Sears Cynthia L. , Goldenring James R. , Franklin Jeffrey L. , Vandekar Simon , Roland Joseph T. , Su Timothy , Huh Won Jae , Liu Qi , Coffey Robert J. , Shrubsole Martha J. , Lau Ken 
Published: January 2021

AbstractMost colorectal cancers (CRCs) develop from either adenomas (ADs) or sessile serrated lesions (SSLs). The origins and molecular landscapes of these histologically distinct pre-cancerous polyps remain incompletely understood. Here, we present an atlas at single-cell resolution of sporadic conventional tubular/tubulovillous ADs, SSLs, hyperplastic polyps (HPs), microsatellite stable (MSS) and unstable (MSI-H) CRC, and normal colonic mucosa. Using single-cell transcriptomics and multiplex imaging, we studied 69 datasets from 33 participants. We also examined separate sets of 66 and 274 polyps for RNA and targeted gene sequencing, respectively. We performed multiplex imaging on a tissue microarray of 14 ADs and 15 CRCs, and we integrated pre-cancer polyp data with published single-cell and The Cancer Genome Atlas (TCGA) bulk CRC data to establish potential polyp-cancer relationships. Striking differences were observed between ADs and SSLs that extended to MSS and MSI-H CRCs, respectively, reflecting their distinct origins and trajectories. ADs arose from WNT pathway dysregulation in stem cells, which aberrantly expanded and expressed a Hippo and ASCL2 regenerative program. In marked contrast, SSLs were depleted of stem cell-like populations and instead exhibited a program of gastric metaplasia in the setting of elevated cytotoxic inflammation. Using subtype-specific gene regulatory networks and shared genetic variant analysis, we implicated serrated polyps, including some HPs conventionally considered benign, as arising from a metaplastic program in committed absorptive cells. ADs and SSLs displayed distinct patterns of immune cell infiltration that may influence their natural history. Our multi-omic atlas provides novel insights into the malignant potential of colorectal polyps and serves as a framework for precision surveillance and prevention of sporadic CRC.
Emergence and Evolution of a Prevalent New SARS-CoV-2 Variant in the United States
Authors: Pater Adrian A. , Bosmeny Michael S. , Barkau Christopher L. , Ovington Katy N. , Chilamkurthy Ramadevi , Parasrampuria Mansi , Eddington Seth B. , Yinusa Abadat O. , White Adam A. , Metz Paige E. , Sylvain Rourke J. , Hebert Madison M. , Benzinger Scott W. , Sinha Koushik , Gagnon Keith T. 
Published: January 2021

AbstractGenomic surveillance can lead to early identification of novel viral variants and inform pandemic response. Using this approach, we identified a new variant of the SARS-CoV-2 virus that emerged in the United States (U.S.). The earliest sequenced genomes of this variant, referred to as 20C-US, can be traced to Texas in late May of 2020. This variant circulated in the U.S. uncharacterized for months and rose to recent prevalence during the third pandemic wave. It initially acquired five novel, relatively unique non-synonymous mutations. 20C-US is continuing to acquire multiple new mutations, including three independently occurring spike protein mutations. Monitoring the ongoing evolution of 20C-US, as well as other novel emerging variants, will be essential for understanding SARS-CoV-2 host adaptation and predicting pandemic outcomes.
The impact of the coronavirus disease 2019 (COVID-19) pandemic on university students’ dietary intake, physical activity, and sedentary behaviour
Authors: Bertrand Leandy , Shaw Keely A. , Ko Jongbum , Deprez Dalton , Chilibeck Philip D. , Zello Gordon A. 
Published: January 2021

AbstractUniversity students are a vulnerable group for poor dietary intake, insufficient physical activity and sedentary behaviour. The purpose of this study was to examine the impact of COVID-19 on university students’ dietary intake, physical activity and sedentary behaviour. Participants were students (n=125) from the Universities of Saskatchewan and Regina. An online questionnaire was administered retrospectively (for pre-pandemic) and prospectively (during the pandemic) to examine students’ dietary intake, physical activity and sedentary behaviour. Overall, nutrient and caloric intakes were significantly reduced (p<0.05) during the pandemic, and alcohol intake increased (p=0.03). Before the pandemic, 16% and 54% of the participants were meeting the Canadian 24-Hour Movement Guidelines for Adults (18–64 years) of 150 minutes of moderate-vigorous physical activity and 8 hours or less of sedentary activity respectively. Only 10% met the guidelines for physical activity while 30% met the guidelines for sedentary behaviour during the pandemic. The minutes per week spent engaging in moderate to vigorous physical activity during the pandemic decreased by approximately 20% (p<0.001). The hours spent in sedentary activities increased by 3 hours per day (p<0.001). Our findings confirm that during the pandemic, students’ inadequate dietary intake, high alcohol consumption, low physical activity and high sedentary behaviour were significantly compounded.NoveltyDuring COVID-19, the nutrient and caloric intakes of university students decreased, and alcohol intake increased significantly.University students’ physical activity levels decreased, and sedentary activity increased significantly during COVID-19.During COVID-19 students did not engage in sufficient physical activity to offset the increased sedentary behaviour.
The Effect of Short Message Service (SMS)-Reminders on Child Health in Parents of Newborns: A Pilot Randomised Controlled Trial
Authors: Shah M , Ramsay J , Dymock M , Marsh J , Newall N , McCallum C , Davis J , Snelling T 
Published: January 2021

AbstractBackgroundIncomplete vaccination in Australia is greatly due to vaccine hesitancy, which is driven by multiple factors. Studies analysing the effect of behavioural ‘nudges’ on vaccine uptake have shown promising results. Although there is some evidence for positively framed SMS vaccine messages, evidence is lacking for loss-based framed messages which may be highly effective but may paradoxically risk increasing vaccine hesitancy. This pilot study aimed to evaluate the effect of loss-based framed SMS messages on vaccine hesitancy.MethodsThis single-blinded randomised controlled trial enrolled pregnant women from antenatal clinics in King Edward Memorial Hospital, Perth, WA which delivers approximately 6000 higher-risk infants per year. Participants were randomised to receive either a loss-based framed SMS message warning of the risks of failure to vaccinate, or a sham SMS message unrelated to vaccination, and were asked to complete the short-scale vaccine hesitancy questionnaire before and after the intervention.DiscussionThe application of behavioural sciences through SMS-reminders has the potential to improve vaccination rates. There are difficulties in engaging with parents of newborns about vaccine hesitancy. Further research is warranted using other approaches to recruitment.HighlightsPilot randomised controlled trial on the use of SMS reminders to influence vaccine hesitancyApplication of behavioural economics, nudge techniques and mobile healthVaccine hesitancy measured using the short-scale PACV questionnaireThere are difficulties in engaging with parents of newborns about vaccine hesitancyFurther research needed to optimise message framing, timing and reduce vaccine hesitancyTrial RegistrationThe trial is registered with the Australia and New Zealand Clinical Trials Register (ACTRN12618001510235).
The SLIM1 transcription factor is required for arsenic resistance inArabidopsis thaliana
Authors: Jobe Timothy O. , Yu Qi , Hauser Felix , Xie Qingqing , Meng Yuan , Maassen Tim , Kopriva Stanislav , Schroeder Julian I. 
Published: January 2021

AbstractThe transcriptional regulators of arsenic-induced gene expression remain largely unknown. Sulfur assimilation is tightly linked with arsenic detoxification. Here we report that mutant alleles in the SLIM1 transcription factor are substantially more sensitive to arsenic than cadmium. Arsenic treatment caused high levels of oxidative stress in theslim1mutants, andslim1alleles were impaired in both thiol and sulfate accumulation. We further found enhanced arsenic accumulation in roots ofslim1mutants. Transcriptome analyses indicate an important role for SLIM1 in arsenic-induced tolerance mechanisms. The present study identifies the SLIM1 transcription factor as an essential component in arsenic tolerance and arsenic-induced gene expression. Our results suggest that the severe arsenic sensitivity of theslim1mutants is caused by altered redox status.
High rates of evolution preceded shifts to sex-biased gene expression inLeucadendron, the most sexually dimorphic angiosperms
Authors: Scharmann Mathias , Rebelo Anthony G , Pannell John R 
Published: January 2021

AbstractThe males and females of many dioecious plants differ in morphological (Dawson and Geber 1999; Barrett and Hough 2013; Tonnabel et al. 2017), physiological (Juvany and Munné-Bosch 2015), life-history (Delph 1999), and defence traits (Cornelissen and Stiling 2005). Ultimately, such sexual dimorphism must largely be due to differential gene expression between the sexes (Ellegren and Parsch 2007), but little is known about how sex-biased genes are recruited and how their expression evolves over time. We measured gene expression in leaves of males and females of ten species sampled across the South African Cape genusLeucadendron, which shows repeated changes in sexual dimorphism and includes the most extreme differences between males and females in flowering plants (Midgley 2010; Barrett and Hough 2013; Tonnabel et al. 2014). Even in the most dimorphic species in our sample, fewer than 2% of genes showed sex-biased gene expression (SBGE) in vegetative tissue, with surprisingly little correspondence between SBGE and vegetative dimorphism across species. The identity of sex-biased genes inLeucadendronwas highly species-specific, with a rapid turnover among species. In animals, sex-biased genes often evolve more quickly than unbiased genes in their sequences and expression levels (Ranz et al. 2003; Khaitovich et al. 2005; Ellegren and Parsch 2007; Voolstra et al. 2007; Harrison et al. 2015; Naqvi et al. 2019), consistent with hypotheses invoking rapid evolution due to sexual selection. Our phylogenetic analysis inLeucadendron, however, clearly indicates that sex-biased genes are recruited from a class of genes with ancestrally rapid rates of expression evolution, perhaps due to low evolutionary or pleiotropic constraints. Nevertheless, we also find evidence for adaptive evolution of expression levels once sex bias evolves. Thus, although the expression of sex-biased genes is ultimately responsive to selection, high rates of expression evolution might usually predate the evolution of sex bias.
Glacial connectivity and current population fragmentation in sky-islands explain the contemporary distribution of genomic variation in two narrow-endemic montane grasshoppers from a biodiversity hotspot
Authors: Tonzo Vanina , Ortego Joaquín 
Published: January 2021

AbstractAimCold-adapted biotas from mid-latitudes often show small population sizes, harbor low levels of local genetic diversity, and are highly vulnerable to extinction due to ongoing climate warming and the progressive shrink of montane and alpine ecosystems. In this study, we use a suite of analytical approaches to infer the demographic processes that have shaped contemporary patterns of genomic variation inOmocestus bolivariandO. femoralis, two narrow-endemic and red-listed Iberian grasshoppers forming highly fragmented populations in the sky island archipelago of the Baetic System.LocationSoutheastern Iberia.MethodsWe quantified genomic variation in the two focal taxa and coupled ecological niche models and a spatiotemporally explicit simulation approach based on coalescent theory to determine the relative statistical support of a suite of competing demographic scenarios representing contemporary population isolation (i.e., a predominant role of genetic drift)vs. historical connectivity and post-glacial colonization of sky islands (i.e., pulses of gene flow and genetic drift linked to Pleistocene glacial cycles).ResultsInference of spatial patterns of genetic structure, environmental niche modelling, and statistical evaluation of alternative species-specific demographic models within an Approximate Bayesian Computation framework collectively supported genetic admixture during glacial periods and postglacial colonization of sky islands, rather than long-term population isolation, as the scenario best explaining the current distribution of genomic variation in the two focal taxa. Moreover, our analyses revealed that isolation in sky islands have also led to extraordinary genetic fragmentation and contributed to reduce local levels of genetic diversity.Main conclusionsThis study exemplifies the potential of integrating genomic and environmental niche modelling data across biological and spatial replicates to determine whether organisms with similar habitat requirements have experienced concerted/idiosyncratic responses to Quaternary climatic oscillations, which can ultimately help to reach more general conclusions about the vulnerability of mountain biodiversity hotspots to ongoing climate warming.
ARID1A-mutant and deficient bladder cancer is sensitive to EZH2 pharmacologic inhibition
Authors: Ferguson James E. , Rehman Hasibur , Chandrashekar Darshan S. , Chakravarthi Balabhadrapatruni V. S. K. , Nepal Saroj , Eich Marie-Lisa , Robinson Alyncia D. , Agarwal Sumit , Hodigere Balasubramanya Sai Akshaya , Naik Gurudatta , Manne Upender , Netto George J , Pan Chong-xian , Sonpavde Guru , Varambally Sooryanarayana 
Published: January 2021

AbstractMetastatic urothelial carcinoma of the bladder is generally incurable by current systemic therapy. Molecular characterization of bladder cancer (BLCa) has revealed multiple candidate driver genes for BLCa tumorigenesis. Epigenetic/chromatin modifiers have been shown to be frequently mutated in BLCa, with ARID1A mutations highly prevalent in nearly 20% of early and late stage tumors. EZH2 is a histone methyltransferase that acts as an oncogene. The data herein show that ARID1A deficient tumors, but not ARID1A wild-type tumors are sensitive to EZH2 inhibition. Specifically, EZH2 inhibitor-treated ARID1A deficient bladder cancer cells show significantly reduced cell viability, colony formation, andin vivotumor growth relative to ARID1A-wild type bladder cancer cells. Thus, our study suggests that a specific subset of bladder cancer patients with ARID1A mutations can be therapeutically treated with pharmacologic inhibitors targeting EZH2.
A method for the efficient iron-labeling of patient-derived xenograft cells and cellular imaging validation
Authors: Knier Natasha N. , Dubois Veronica P. , Ronald John A. , Foster Paula J. 
Published: January 2021

AbstractThere is momentum towards implementing patient-derived xenograft models (PDX) in cancer research to reflect the histopathology, tumour behavior, and metastatic properties observed in the original tumour. These models are more predictive of clinical outcomes and are superior to cell lines for preclinical drug evaluation and therapeutic strategies. To study PDX cells preclinically, we used both bioluminescence imaging (BLI) to evaluate cell viability and magnetic particle imaging (MPI), an emerging imaging technology to allow for detection and quantification of iron nanoparticles. The goal of this study was to develop the first successful iron labeling method of breast cancer cells derived from patient brain metastases and validate this method with imaging during tumour development.Luciferase expressing human breast cancer PDX cells (F2-7) were successfully labeled after incubation with micron-sized iron oxide particles (MPIO; 25 μg Fe/mL). NOD/SCID/ILIIrg-/-(n=5) mice received injections of 1×106iron-labeled F2-7 cells into the fourth mammary fat pad (MFP). BLI was performed longitudinally to day 49 and MPI was performed up to day 28.In vivoBLI revealed that signal increased over time with tumour development. MPI revealed decreasing signal in the tumours and increasing signal in the liver region over time.Here, we demonstrate the first application of MPI to monitor the growth of a PDX MFP tumour. To accomplish this, we also demonstrate the first successful labeling of PDX cells with iron oxide particles. Imaging of PDX cells provides a powerful system to better develop personalized therapies targeting breast cancer brain metastasis.
Taxonomy, distribution and host relationships of aphidiine wasps (Hymenoptera: Aphidiidae) parasitizing aphids (Hemiptera: Aphididae) in Australian grain production landscapes
Authors: Ward Samantha , Umina Paul A. , Polaszek Andrew , Hoffmann Ary A. 
Published: January 2021

AbstractAphid parasitoids (Hymenoptera; Aphidiidae) were surveyed within grain production landscapes in Victoria, Australia between 2017 and 2018, as well as more sporadically nationwide between 2016 and 2019. In addition, aphidiine records were collated from insect depositories around Australia and online databases. The 5551 specimens recorded constituted a total of 23 species and seven genera.Diaeretiella rapae(M’Intosh) was the most common species, representing more than 70% of all aphidiines recorded. This species also showed a greater northerly geographic range than other aphidiines. During sampling between 2017 and 2019, aphidiines were reared from mummies to ascertain host-parasitoid relationships.Diaeretiella rapaewas again the most commonly reared parasitoid, although aphidiine preference varied with aphid host and between states and territories. An illustrated dichotomous key to Australian aphidiines in grain production landscapes is provided for the 11 species sampled in our field surveys. This is the first comprehensive review of aphidiines sampled within Australia in over two decades. Knowledge about the diversity and distribution of these parasitoids is important for understanding their impact on current and future invasions of aphid species. In addition, understanding the interactions between grain aphids and their associated parasitoids will further support the inclusion of parasitoid wasps into integrated pest management (IPM) strategies.
Dimensionality reduction by UMAP reinforces sample heterogeneity analysis in bulk transcriptomic data
Authors: Yang Yang , Sun Hongjian , Zhang Yu , Zhang Tiefu , Gong Jialei , Wei Yunbo , Duan Yong-Gang , Shu Minglei , Yang Yuchen , Wu Di , Yu Di 
Published: January 2021

AbstractTranscriptome profiling and differential gene expression constitute a ubiquitous tool in biomedical research and clinical application. Linear dimensionality reduction methods especially principal component analysis (PCA) are widely used in detecting sample-to-sample heterogeneity in bulk transcriptomic datasets so that appropriate analytic methods can be used to correct batch effects, remove outliers and distinguish subgroups. In response to the challenge in analysing transcriptomic datasets with large sample size such as single-cell RNA-sequencing (scRNA-seq), non-linear dimensionality reduction methods were developed. t-distributed stochastic neighbour embedding (t-SNE) and uniform manifold approximation and projection (UMAP) show the advantage of preserving local information among samples and enable effective identification of heterogeneity and efficient organisation of clusters in scRNA-seq analysis. However, the utility of t-SNE and UMAP in bulk transcriptomic analysis has not been carefully examined. Therefore, we compared major dimensionality reduction methods (linear: PCA; nonlinear: multidimensional scaling (MDS), t-SNE, and UMAP) in analysing 71 bulk transcriptomic datasets with large sample sizes. UMAP was found superior in preserving sample level neighbourhood information and maintaining clustering accuracy, thus conspicuously differentiating batch effects, identifying pre-defined biological groups and revealing in-depth clustering structures. We further verified that new clustering structures visualised by UMAP were associated with biological features and clinical meaning. Therefore, we recommend the adoption of UMAP in visualising and analysing of sizable bulk transcriptomic datasets.
An optimized stepwise algorithm combining rapid antigen and RT-qPCR for screening of COVID-19 patients
Authors: Halfon Philippe , Penaranda Guillaume , Khiri Hacène , Garcia Vincent , Drouet Hortense , Philibert Patrick , Psomas Christina , Delord Marion , Allemand-Sourrieu Julie , Retornaz Frédérique , Charpin Caroline , Gonzales Thomas , Pegliasco Hervé , Allardet-Servent Jérôme 
Published: January 2021

AbstractBackgroundDiagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.MethodsFrom August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.ResultsThe overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.ConclusionThis study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.