bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy and chemotherapy alter migration of brain cancer cells before cell death
Authors: Merrick Michael , Mimlitz Michael J. , Weeder Catherine , Akhter Haris , Bray Allie , Walther Andrew , Nwakama Chisom , Bamesberger Joe , Djam Honour , Abid Kaamil , Ekpenyong Andrew 
Published: July 2020

AbstractAlthough radiotherapy and most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis strategies alongside chemotherapy and radiotherapy. An important step in the metastatic cascade is migration. It is the first step in metastasis via local invasion. Here we address the question whether ionizing radiation and/or chemotherapy might inadvertently promote metastasis and/or invasiveness by enhancing cell migration. We used a standard laboratory irradiator, Faxitron CellRad, to irradiate both non-cancer (HCN2 neurons) and cancer cells (T98G glioblastoma) with 2 Gy, 10 Gy and 20 Gy of X-rays. Paclitaxel (5 μM) was used for chemotherapy. We then measured the attachment and migration of the cells using an electric cell substrate impedance sensing device. Both the irradiated HCN2 cells and T98G cells showed significantly (p < 0.01) enhanced migration compared to non-irradiated cells, within the first 20 to 40 hours following irradiation with 20 Gy. Our results suggest that cell migration should be a therapeutic target in anti-metastasis/anti-invasion strategies for improved radiotherapy and chemotherapy outcomes.
Requirement of the antimicrobial peptide CRAMP for macrophages to eliminate phagocytosedE. colithrough an autophagy pathway
Authors: Chen Keqiang , Yoshimura Teizo , Gong Wanghua , Tian Cuimeng , Huang Jiaqiang , Trinchier Giorgio , Wang Ji Ming 
Published: July 2020

AbstractHost-derived antimicrobial peptides play an important role in the defense against extracellular bacterial infections. However, the capacity of antimicrobial peptides derived from macrophages as potential antibacterial effectors against intracellular pathogens remains unknown. In this study, we report that normal (wild type, WT) mouse macrophages increased their expression of the cathelicidin-related antimicrobial peptide (CRAMP) after infection by viableE. colior stimulation with inactivatedE. coliand its product LPS, a process involving activation of NF-κB followed by protease-dependent conversion of CRAMP from an inactive precursor to an active form. The active CRAMP was required by WT macrophages to eliminate phagocytosedE. coli, with participation of autophagy-related proteins ATG5, LC3-II, and LAMP-1 as well as conjugation of the bacteria with p62. The autophagy-mediated elimination ofE. coliwas impaired inCRAMP−/−macrophages resulting in retention of intracellular bacteria and fragmentation of macrophages. These results indicate CRAMP as a critical component in autophagy-mediated clearance of intracellularE. coliby macrophages.
Scoping reviews in medical education: A scoping review
Authors: Maggio Lauren A. , Larsen Kelsey , Thomas Aliki , Costello Joseph A. , Artino Anthony R. 
Published: July 2020

AbstractPurposeThe purpose of this study was to characterize the extent, range, and nature of scoping reviews published in core medical education journals. In so doing, the authors identify areas for improvement in the conduct and reporting of scoping reviews, and highlight opportunities for future research.MethodThe authors searched PubMed for scoping reviews published between 1999 through April 2020 in 14 medical education journals. From each review, the authors extracted and summarized key bibliometric data, the rationales given for conducting a scoping review, the research questions, and key reporting elements as described in the PRISMA-ScR reporting guidelines. Rationales and research questions were mapped to the reasons for conducting a scoping review, as described by Arksey and O’Malley.ResultsOne hundred and one scoping reviews were included. On average 10.1 scoping reviews (MED=4, SD=13.08) were published annually with the most reviews published in 2019 (n=42) in 13 of the included 14 journals reviewed.Academic Medicinepublished the most scoping reviews (n=28) overall. Authors described multiple reasons for undertaking scoping reviews, including to: summarize and disseminate research findings (n=77); examine the extent, range, and nature of research activity in a given area (n=74); and to analyze an emerging topic or heterogenous literature base (n=46). In 11 reviews there was alignment between the rationales for the scoping review and the stated research questions. No review addressed all elements of the PRISMA-ScR, with only a minority of authors publishing a protocol (n=2) or including stakeholders (n=20). Authors identified several shortcomings of scoping review methodology, including being unable to critically assess the included studies.ConclusionsMedical educators are increasingly conducting scoping reviews with a desire to characterize the literature on a topic. There is room for improvement in the reporting of scoping reviews, including the alignment of research questions, the creation and publishing of protocols, and the inclusion of external stakeholders in published works.
An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype
Authors: Keough Kathleen C. , Shah Parisha P. , Gjoni Ketrin , Santini Garrett T. , Wickramasinghe Nadeera M. , Dundes Carolyn E. , Karnay Ashley , Chen Angela , Salomon Rachel E.A. , Walsh Patrick J. , Nguyen Son C. , Whalen Sean , Joyce Eric F. , Loh Kyle M. , Dubois Nicole , Pollard Katherine S. , Jain Rajan 
Published: July 2020

AbstractAssociation of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamin-associated domains (LADs) have yet to be mapped genome-wide in a diverse panel of human cell types, which has limited our understanding of the role peripheral chromatin plays in development and disease. To address this gap, we mapped LAMIN B1 (LB1) across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas of peripheral chromatin with publicly available genomic data, as well as gene expression and repressive histone maps generated for this study, revealed that in all twelve cellular contexts lamin-associated chromatin is organized into at least two subtypes defined by differences in LB1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Most genes gain or lose LB1 occupancy consistent with their cell type along developmental trajectories; however, we also identified examples where the enhancer, but not the gene body and promoter, change LAD state. Imaging of fluorescently labeled DNA in single cells validated these transitions and showed intermediate radial positioning of LADs that are gene dense, relatively accessible, and dynamic across development. This atlas represents the largest resource to date for peripheral chromatin organization studies.
Elucidation of cryptic and allosteric pockets within the SARS-CoV-2 protease
Authors: Sztain Terra , Amaro Rommie , McCammon J. Andrew 
Published: July 2020

AbstractThe SARS-CoV-2 pandemic has rapidly spread across the globe, posing an urgent health concern. Many quests to computationally identify treatments against the virus rely on in silico small molecule docking to experimentally determined structures of viral proteins. One limit to these approaches is that protein dynamics are often unaccounted for, leading to overlooking transient, druggable conformational states. Using Gaussian accelerated molecular dynamics to enhance sampling of conformational space, we identified cryptic pockets within the SARS-CoV-2 main protease, including some within regions far from the active site and assed their druggability. These pockets can aid in virtual screening efforts to identify a protease inhibitor for the treatment of COVID-19.Abstract Figure
The trajectory of cortical GABA levels across the lifespan: An individual participant data meta-analysis of edited MRS studies
Authors: Porges Eric C. , Jensen Greg , Foster Brent , Edden Richard A. E. , Puts Nicolaas A. J. 
Published: July 2020

ABSTRACTGABA is the principal inhibitory neurotransmitter in the human brain and can be measured with Magnetic Resonance Spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age-range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, 8 suitable datasets were integrated to generate a model of the trajectory of GABA across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show the lifespan trajectory of GABA involves an early period of rapid increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.
Unveiling transposable element expression heterogeneity in cell fate regulation at the single-cell level
Authors: He Jiangping , Babarinde Isaac A. , Sun Li , Xu Shuyang , Chen Ruhai , Wei Yuanjie , Li Yuhao , Ma Gang , Zhuang Qiang , Hutchins Andrew P. , Chen Jiekai 
Published: July 2020

AbstractTransposable elements (TEs) make up a majority of a typical eukaryote’s genome, and contribute to cell heterogeneity and fate in unclear ways. Single cell-sequencing technologies are powerful tools to explore cells, however analysis is typically gene-centric and TE activity has not been addressed. Here, we developed a single-cell TE processing pipeline, scTE, and report the activity of TEs in single cells in a range of biological contexts. Specific TE types were expressed in subpopulations of embryonic stem cells and were dynamically regulated during pluripotency reprogramming, differentiation, and embryogenesis. Unexpectedly, TEs were expressed in somatic cells, including human disease-specific TEs that are undetectable in bulk analyses. Finally, we applied scTE to single cell ATAC-seq data, and demonstrate that scTE can discriminate cell type using chromatin accessibly of TEs alone. Overall, our results reveal the dynamic patterns of TEs in single cells and their contributions to cell fate and heterogeneity.
Retinoic acid rewires the adrenergic core regulatory circuitry of childhood neuroblastoma
Authors: Zimmerman Mark W. , Durbin Adam D. , He Shuning , Oppel Felix , Shi Hui , Tao Ting , Li Zhaodong , Berezovskaya Alla , Liu Yu , Zhang Jinghui , Young Richard A. , Abraham Brian J. , Look A. Thomas 
Published: July 2020

AbstractNeuroblastoma cell identity depends on a core regulatory circuit (CRC) of transcription factors that collaborate withMYCNto drive the oncogenic gene expression program. For neuroblastomas dependent on the adrenergic CRC, treatment with retinoids can inhibit cell growth and induce differentiation. Here we show that whenMYCN-amplified neuroblastomas cells are treated with retinoic acid, histone H3K27 acetylation and methylation become redistributed to decommission super-enhancers driving the expression ofPHOX2BandGATA3, together with the activation of new super-enhancers that drive high levels ofMEIS1andSOX4expression. These findings indicate that treatment with retinoids can reprogram the enhancer landscape, resulting in downregulation ofMYCNexpression, while establishing a new retino-sympathetic CRC that causes proliferative arrest and sympathetic differentiation. Thus, we provide mechanisms that account for the beneficial effects of retinoids in high-risk neuroblastoma and explain the rapid downregulation of expression ofMYCNdespite massive levels of amplification of this gene.
Microrisk Lab: an online freeware for predictive microbiology
Authors: Liu Yangtai , Wang Xiang , Liu Baolin , Dong Qingli 
Published: July 2020

AbstractMicrorisk Lab was designed as an interactive modeling freeware to realize parameter estimation and model simulation in predictive microbiology. This tool was developed based on the R programming language and ‘Shinyapps.io’ server, and designed as a fully responsive interface to the internet-connected devices. A total of 36 peer-reviewed models were integrated for parameter estimation (including primary models of bacterial growth/ inactivation under static and non-isothermal conditions, secondary models of specific growth rate, and competition models of two-flora growth) and model simulation (including integrated models of deterministic or stochastic bacterial growth/ inactivation under static and non-isothermal conditions) in Microrisk Lab. Each modeling section was designed to provide numerical and graphical results with comprehensive statistical indicators depending on the appropriate dataset and/ or parameter setting. In this research, six case studies were reproduced in Microrisk Lab and compared in parallel to DMFit, GInaFiT, IPMP 2013/ GraphPad Prism, Bioinactivation FE, and @Risk, respectively. The estimated and simulated results demonstrated that the performance of Microrisk Lab was statistically equivalent to that of other existing modeling system in most cases. Microrisk Lab allowed for uniform user experience to implement microbial predictive modeling by its friendly interfaces, high-integration, and interconnectivity. It might become a useful tool for the microbial parameter determination and behavior simulation. Non-commercial users could freely access this application athttps://microrisklab.shinyapps.io/english/.
Severe corrosion of carbon steel in oil field produced water can be linked to methanogenic archaea containing a special type of [NiFe] hydrogenase
Authors: Lahme Sven , Mand Jaspreet , Longwell John , Smith Ramsey , Enning Dennis 
Published: July 2020

ABSTRACTMethanogenic archaea have long been implicated in microbially influenced corrosion (MIC) of oil and gas infrastructure, yet a first understanding of the underlying molecular mechanisms has only recently emerged. We surveyed pipeline-associated microbiomes from geographically distinct oil field facilities and found methanogens to account for 0.2 – 9.3% of the sequenced communities. Neither the type nor the abundance of the detected methanogens correlated to the perceived severity of MIC in these pipelines. Using fluids from one pipeline, MIC was reproduced in the laboratory, both under stagnant conditions and in customized corrosion reactors simulating pipeline flow. High corrosion rates (up to 2.43 mm Fe0yr−1) with macroscopic, localized corrosion features were attributed to lithotrophic, mesophilic microbial activity. Other laboratory tests with the same waters yielded negligible corrosion rates (< 0.08 mm Fe0yr−1). Recently a novel [NiFe] hydrogenase, fromMethanococcus maripaludisstrain OS7, was demonstrated to accelerate corrosion. We developed a specific qPCR assay and detected the gene encoding the large subunit of this hydrogenase (labelledmicH) in corrosive (> 0.15 mm Fe0yr−1) biofilms. ThemicHgene on the other hand was absent in non-corrosive biofilms despite an abundance of methanogens. Reconstruction of a nearly completeMethanococcus maripaludisgenome from a highly corrosive mixed biofilm revealedmicHand associated genes in near-identical genetic configuration as strain OS7, thereby supporting our hypothesis that the encoded molecular mechanism contributed to corrosion. Lastly, the proposed MIC biomarker was detected in multiple oil fields, indicating a geographically widespread involvement of this [NiFe] hydrogenase in MIC.IMPORTANCEMicroorganisms can deteriorate built environments, which is particularly problematic in the case of pipelines transporting hydrocarbons to industrial end users. MIC is notoriously difficult to detect and monitor and as a consequence, is a particularly difficult corrosion mechanism to manage. Despite the advent of molecular tools and improved microbial monitoring strategies for oil and gas operations, specific underlying MIC mechanisms in pipelines remain largely enigmatic. Emerging mechanistic understanding of methanogenic MIC derived from pure culture work allowed us to develop a qPCR assay that distinguishes technically problematic from benign methanogens in a West African oil field. Detection of the same gene in geographically diverse samples from North America hints at the widespread applicability of this assay. The research presented here offers a step towards a mechanistic understanding of biocorrosion in oil fields and introduces a binary marker for (methanogenic) MIC that can find application in corrosion management programs in industrial settings.
Metabolic Biomarkers for Peripheral Artery Disease Compared with Coronary Artery Disease: Lipoprotein and metabolite profiling of 31,657 individuals from five prospective cohorts
Authors: Tikkanen Emmi , Jägerroos Vilma , Rodosthenous Rodosthenis , Holmes Michael V , Sattar Naveed , Ala-Korpela Mika , Jousilahti Pekka , Lundqvist Annamari , Perola Markus , Salomaa Veikko , Würtz Peter 
Published: July 2020

AbstractBackgroundPeripheral artery disease (PAD) and coronary artery disease (CAD) represent atherosclerosis in different vascular beds. We conducted detailed metabolic profiling to identify biomarkers for the risk of developing PAD and compared with risk of CAD to explore common and unique risk factors for these different vascular diseases.MethodsWe measured blood biomarkers using nuclear magnetic resonance metabolomics in five Finnish prospective general-population cohorts (FINRISK 1997, 2002, 2007, 2012, and Health 2000 studies, n = 31 657). We used Cox modelling to estimate associations between biomarkers and incident symptomatic PAD and CAD (498 and 2073 events, respectively) during median follow-up time of 14 years.ResultsThe pattern of biomarker associations for incident PAD deviated from that for CAD. Apolipoproteins and cholesterol measures were robustly associated with incident CAD (for example, age- and sex-adjusted hazard ratio per SD for higher apolipoprotein B/A-1 ratio: 1.30; 95% confidence interval 1.25-1.36), but not with incident PAD (1.04; 0.95-1.14; Pheterogeneity<0.001). Low-density lipoprotein (LDL) particle concentrations were also associated with incident CAD (e.g. small LDL particles: 1.24; 1.19-1.29) but not with PAD (1.07; 0.98-1.17; Pheterogeneity<0.001). In contrast, more consistent associations of smaller LDL particle size and higher triglyceride levels in LDL and HDL particles with increased risk for both CAD and PAD events were seen (Pheterogeneity>0.05). Many non-traditional biomarkers, including fatty acids, amino acids, inflammation- and glycolysis-related metabolites were associated with future PAD events. Lower levels of linoleic acid, an omega-6 fatty acid, and higher concentrations of glucose, lactate, pyruvate, glycerol and glycoprotein acetyls were more strongly associated with incident PAD as compared to CAD (Pheterogeneity<0.001). The differences in metabolic biomarker associations for PAD and CAD remained when adjusting for body mass index, smoking, prevalent diabetes, and medications.ConclusionsThe metabolic biomarker profile for future PAD risk is largely distinct from that of CAD. This may represent pathophysiological differences and may facilitate risk prediction.
Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis
Authors: Leek Nicola J. , Kreilkamp Barbara A. K. , Neason Mollie , de Bezenac Christophe , Ziso Besa , Elkommos Samia , Das Kumar , Marson Anthony G. , Keller Simon S. 
Published: July 2020

AbstractBackgroundPatients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures.MethodsEighty-two patients with NDfE and 40 healthy controls underwent MRI scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis.ResultsVolume of the left hippocampus (P(FDR-corr) = 0.04) and left (P(FDR-corr) = 0.002) and right (P(FDR-corr) = 0.04) thalamus were significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% individual patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy.ConclusionsVolumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.
Effect of manual and digital contact tracing on COVID-19 outbreaks: a study on empirical contact data
Authors: Barrat A. , Cattuto C. , Kivelä M. , Lehmann S. , Saramäki J. 
Published: July 2020

ABSTRACTIn the fight against the COVID-19 pandemic, lockdowns have succeeded in limiting contagions in many countries, at however heavy societal costs: more targeted non-pharmaceutical interventions are desirable to contain or mitigate potential resurgences. Contact tracing, by identifying and quarantining people who have been in prolonged contact with an infectious individual, has the potential to stop the spread where and when it occurs, with thus limited impact. The limitations of manual contact tracing (MCT), due to delays and imperfect recall of contacts, might be compensated by digital contact tracing (DCT) based on smartphone apps, whose impact however depends on the app adoption. To assess the efficiency of such interventions in realistic settings, we use here datasets describing contacts between individuals in several contexts, with high spatial and temporal resolution, to feed numerical simulations of a compartmental model for COVID-19. We find that the obtained reduction of epidemic size has a robust behavior: this benefit is linear in the fraction of contacts recalled during MCT, and quadratic in the app adoption, with no threshold effect. The combination of tracing strategies can yield important benefits, and the cost (number of quarantines) vs. benefit curve has a typical parabolic shape, independent on the type of tracing, with a high benefit and low cost if app adoption and MCT efficiency are high enough. Our numerical results are qualitatively confirmed by analytical results on simplified models. These results may inform the inclusion of MCT and DCT within COVID-19 response plans.