bluuebunny/crossref_metadata_2025 huggingface dataset:
A Feedback Mechanism RegulatesOdorant ReceptorExpression in the Malaria Mosquito,Anopheles gambiae
Authors: Maguire Sarah E. , Afify Ali , Goff Loyal A. , Potter Christopher J.
Published: July 2020

Mosquitoes locate and approach humans (‘host-seek’) when specific Olfactory Neurons (ORNs) in the olfactory periphery activate a specific combination of glomeruli in the mosquito Antennal Lobe (AL). We hypothesize that dysregulating proper glomerular activation in the presence of human odor will prevent host-seeking behavior. In experiments aimed at ectopically activating most ORNs in the presence of human odor, we made a surprising finding: ectopic expression of anAgOr (AgOr2)inAnopheles gambiaeORNs dampens the activity of the expressing neuron. This contrasts studies inDrosophila melanogaster, the typical insect model of olfaction, in which ectopic expression of non-native ORs in ORNs confers ectopic neuronal responses without interfering with native olfactory physiology. To gain insight into this dysfunction in mosquitoes, RNA-seq analyses were performed comparing wild-type antennae to those ectopically expressingAgOr2in ORNs. Remarkably, almost allOrtranscripts were significantly downregulated (except forAgOr2), and additional experiments suggest that it is AgOR2 protein rather than mRNA that mediates this downregulation. Our study shows that ORNs ofAnophelesmosquitoes (in contrast toDrosophila) employ a currently unexplored regulatory mechanism of OR expression, which may be adaptable as a vector-control strategy.

SIGNIFICANCE STATEMENT

Studies inDrosophila melanogastersuggest that insect Olfactory Receptor Neurons (ORNs) do not contain mechanisms by which Odorant Receptors (ORs) regulate OR expression. This has proved useful in studies where ectopic expression of an OR inDrosophilaORNs confers responses to the odorants that activate the newly expressed OR. In experiments inAnopheles gambiaemosquitoes, we found that ectopic expression of an OR in mostAnophelesORNs dampened the activity of the expressing neurons. RNA-seq analyses demonstrated that ectopic OR expression inAnophelesORNs leads to downregulation of endogenousOrtranscripts. Additional experiments suggest that this downregulation required ectopic expression of a functional OR protein. These findings reveal thatAnophelesmosquitoes, in contrast toDrosophila, contain a feedback mechanism to regulate OR expression. Mosquito ORNs might employ regulatory mechanisms of OR expression previously thought to occur only in non-insect olfactory systems.
Kilohertz retinal FF-SS-OCT and flood imaging with hardware-based adaptive optics
Authors: Valente Denise , Vienola Kari V. , Zawadzki Robert J. , Jonnal Ravi S.
Published: July 2020

A retinal imaging system was designed for full-field (FF) swept-source (SS) optical coherence tomography (OCT) with cellular resolution. The system incorporates a real-time adaptive optics (AO) subsystem and a very high speed CMOS sensor, and is capable of acquiring volumetric images of the retina at rates up to 1 kHz. While digital aberration correction (DAC) is an attractive potential alternative to AO, it has not yet been shown to provide resolution of cones in the fovea, where early detection of functional deficits is most critical. Here we demonstrate that FF-SS-OCT with hardware AO permits resolution of foveal cones, with volume rates adequate to measure light-evoked changes in photoreceptors. With the reference arm blocked, the system can operate as kilohertz AO flood illumination fundus camera with adjustable temporal coherence and is expected to allow measurement of light-evoked changes caused by common path interference in photoreceptor outer segments (OS). In this work, we describe the system’s optical design, characterize its performance, and demonstrate its ability to produce images of the human photoreceptor mosaic.
Multi-Platform Assessment of DNA Sequencing Performance using Human and Bacterial Reference Genomes in the ABRF Next-Generation Sequencing Study
Authors: Foox Jonathan , Tighe Scott W. , Nicolet Charles M. , Zook Justin M. , Byrska-Bishop Marta , Clarke Wayne E. , Khayat Michael M. , Mahmoud Medhat , Laaguiby Phoebe K. , Herbert Zachary T. , Warner Derek , Grills George S. , Jen Jin , Levy Shawn , Xiang Jenny , Alonso Alicia , Schroth Gary P. , Sedlazeck Fritz J. , Narzisi Giuseppe , Farmerie William , Baldwin Don A. , Mason Christopher E.
Published: July 2020

Massively parallel DNA sequencing is a critical tool for genomics research and clinical diagnostics. Here, we describe the Association of Biomolecular Resource Facilities (ABRF) Next-Generation Sequencing Phase II Study to measure quality and reproducibility of DNA sequencing. Replicates of human and bacterial reference DNA samples were generated across multiple sequencing platforms, including well-established technologies such as Illumina, ThermoFisher Ion Torrent, and Pacific Biosciences, as well as emerging technologies such as BGI, Genapsys, and Oxford Nanopore. A total of 202 datasets were generated to investigate the performance of a total of 16 sequencing platforms, including mappability of reads, coverage and error rates in difficult genomic regions, and detection of small-scale polymorphisms and large-scale structural variants. This study provides a comprehensive baseline resource for continual benchmarking as chemistries, methods, and platforms evolve for DNA sequencing.
Novel rabies virus variant for bi-directional optical control reveals modulatory influence of the pulvinar on visual cortex in rat
Authors: Scholl LR , Zhang L , Foik AT , Lyon DC
Published: July 2020

Optogenetic tools have become of great utility in the causal analysis of systems in the brain. However, current optogenetic techniques do not reliably support both excitation and suppression of the same cells in vivo, limiting analysis and slowing research. Here we developed a novel glycoprotein-deleted rabies virus expressing two channelrhodopsin proteins, GtACR2 and Chrimson, in order to independently manipulate excitatory and inhibitory transmembrane potentials, respectively. Using this approach, we demonstrated that rodent pulvinar neurons modulate cortical size tuning and suppress flash responses, but do not drive activity in visual cortex. While our goal was primarily to develop this novel method to study the structure-function organization of thalamocortical circuits, this technique is readily applicable to study any brain region.
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

Although 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.
Deep ubiquitination site profiling by single-shot data-independent acquisition mass spectrometry
Authors: Steger Martin , Ihmor Phillip , Backman Mattias , Müller Stefan , Daub Henrik
Published: July 2020

We report a highly optimized proteomics method for in-depth ubiquitination profiling, which combines efficient protein extraction and data-independent acquisition mass spectrometry (DIA-MS). Employing DIA for both spectral library generation and single-shot sample analysis, we quantify up to 70,000 ubiquitinated peptides per MS run with high precision, data completeness and throughput. Our approach resolves the dynamics of ubiquitination and protein degradation with an unprecedented analytical depth.
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

Host-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

Purpose

The 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.

Method

The 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.

Results

One 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.

Conclusions

Medical 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

Association 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

The 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

GABA 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

Transposable 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

Neuroblastoma 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

Microrisk 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

Methanogenic 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.

IMPORTANCE

Microorganisms 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

Background

Peripheral 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.

Methods

We 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.

Results

The 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.

Conclusions

The 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

Background

Patients 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.

Methods

Eighty-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.

Results

Volume 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.

Conclusions

Volumetric 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

In 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.
A multinational e-survey on the delivery of cardiology services in Africa during the COVID-19 pandemic: what should we expect after this pandemic?
Authors: Nganou-Gnindjio Chris Nadege , Temgoua Mazou Ngou , Kuate Liliane Mfeukeu , Nkoke Clovis , Tochie Joel Noutakdie , Ndobo-Kue Valerie , Owona-Nsiaguam Amalia , Boombhi Jerome , Kipenge Richie , Huba Urbain , Kane Malick , el Jirari Mohamed Taha , Ndongo-Amougou Sylvie , Hamadou Bâ , Menanga Alain , Kingue Samuel
Published: July 2020

Objective

To evaluate the impact of the COVID-19 pandemic on the delivery of cardiology services in Africa.

Design

Cross-sectional e-survey study.

Setting

African countries

Participants

Cardiologists

Primary and Secondary outcomes measures

The primary outcome was the change in service delivery in African cardiology units during the on-going COVID-19 pandemic. The secondary outcomes were the satisfaction of cardiologists with regards to the workload and factors associated with this satisfaction.

Results

There was a significant reduction in working time and the number of patients consulted by week during this pandemic (p<0.001). In general, there was a decrease in the overall activities in cardiovascular care delivery. The majority of cardiology services (76.5%) and consulting programs (85%) were adjusted to the pandemic. Only half of the participants were satisfied with their workload. Reconfiguration of the consultation schedule was associated with a reduced satisfaction of participants (p=0.02).

Conclusions

COVID-19 is associated with an overall reduction in cardiology services rendered in Africa. Since the cardiovascular burdens continue to increase in this part of the World and the risk of cardiovascular complications linked to SARS COV2 remains unchanged cardiology, departments in Africa should anticipate a significant surge of cardiology services demanded by patients after the COVID-19 pandemic.

Strengths and limitations of this study

The study is one of the first African studies to report the impact of the COVID-19 pandemic on the delivery of cardiology services which are very important for Africans given the high prevalence of cardiovascular diseases in this continent.

The multinational design of the study leading to the inclusion of 14 African countries makes the results generalizable to the entire African.

The cross-sectional design of the study represents a major limitation as it remains impossible to either infer causality or untangle bi-directional relationships between the reduction of the delivery in cardiology services and the pandemic or participants’ satisfaction.

Also, the e-survey was drawn in English and this might have restricted the participation by some non-English African respondents due to the language barrier. Hence, perhaps contributing to the relatively small sample size of the study.
Calibration-free regional RF shims for MR spectroscopy
Authors: Berrington Adam , Považan Michal , Mirfin Christopher , Bawden Stephen , Park Young Woo , Marsh Daniel C. , Bowtell Richard , Gowland Penny
Published: July 2020

Purpose

Sufficient control of the RF transmit field (B1+) in small regions-of-interest (ROIs) is critical for single voxel MR spectroscopy at ultra-high field. Static RF shimming, using parallel transmit (pTx), can improve B1+, but must be calibrated for each participant and ROI, which limits its applicability. Additionally, specific-absorption-rate (SAR) becomes hard to predict. This work aimed to find RF shims, which can be applied to any participant, to produce the desired |B1+| within pre-defined target ROIs.

Methods

RF shims were found offline by joint-optimisation on a database, comprising B1+ maps from 11 subjects, considering ROIs in occipital cortex, hippocampus and posterior-cingulate, as well as the whole brain. The B1+ magnitude achieved using calibration-free RF shims was compared to a tailored shimming approach, and MR spectra were acquired using tailored and calibration-free RF shimming in 4 participants. Global and local 10g SAR deposition were modelled.

Results

Calibration-free RF shims resulted in similar |B1+| in small ROIs compared to tailored shimming, in addition to producing spectra of excellent quality and equivalent SNR. Only a small database size was required. SAR deposition was reduced compared to operating in quadrature mode for all ROIs.

Conclusion

This work demonstrates that static RF shims, optimised offline for small regions in single voxel MRS, avoid the need for lengthy B1+ mapping and pTx optimisation for each ROI and participant. Furthermore, power settings may be increased when using calibration-free shims to better take advantage of the flexibility provided by RF shimming for regional acquisition at ultra-high field.
Strategies to reduce the risk of SARS-CoV-2 re-introduction from international travellers
Authors: Clifford Samuel , Quilty Billy J. , Russell Timothy W. , Liu Yang , Chan Yung-Wai Desmond , Pearson Carl A. B. , Eggo Rosalind M. , Endo Akira ,   CMMID COVID-19 Working Group, Flasche Stefan , Edmunds W. John
Published: July 2020

To mitigate SARS-CoV-2 transmission risks from international travellers, many countries currently use a combination of up to 14 days of self-quarantine on arrival and testing for active infection. We used a simulation model of air travellers arriving to the UK from the EU or the USA and the timing of their stages of infection to evaluate the ability of these strategies to reduce the risk of seeding community transmission. We find that a quarantine period of 8 days on arrival with a PCR test on day 7 (with a 1-day delay for test results) can reduce the number of infectious arrivals released into the community by a median 94% compared to a no quarantine, no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median 99% reduction). Shorter quarantine periods still can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (the mean incubation period) in quarantine and have at least one negative test before release are highly effective (e.g. a test on day 5 with release on day 6 results in a median 88% reduction in transmission potential). Without intervention, the current high prevalence in the US (40 per 10,000) results in a higher expected number of infectious arrivals per week (up to 23) compared to the EU (up to 12), despite an estimated 8 times lower volume of travel in July 2020.

Requiring a 14-day quarantine period likely results in less than 1 infectious traveller each entering the UK per week from the EU and the USA (97.5th percentile). We also find that on arrival the transmission risk is highest from pre-symptomatic travellers; quarantine policies will shift this risk increasingly towards asymptomatic infections if eventually-symptomatic individuals self-isolate after the onset of symptoms. As passenger numbers recover, strategies to reduce the risk of re-introduction should be evaluated in the context of domestic SARS-CoV-2 incidence, preparedness to manage new outbreaks, and the economic and psychological impacts of quarantine.
Dental caries among the elderly in Iran: a meta-analysis
Authors: Shoaee Shervan , Sharifi Farshad , Parsa Pooneh Ghavidel , Sofi-Mahmudi Ahmad
Published: July 2020

Objectives

To conduct a systematic review and meta-analysis on dental caries among the elderly in Iran.

Background

The prevalence of dental caries among elderly is high worldwide, and the major burden of oral diseases is caused by dental caries.

Methods

Systematic review of the published and grey literature performed. Six international and local databases used to provide the most comprehensive population-based studies. National oral health surveys, as well as national disease and health surveys considered as other primary sources of data. Quality of remained studies was assessed by a modified tool designed based on STROBE statement checklist to evaluate the cross-sectional studies. The target population was 65+-year-olds Iranian population.

Results

Overall, 917 English articles who those reported dental caries among all age groups were found in international databases and 2138 Persian articles were found in Iranian databases. After quality assessment, and excluding other age groups, 46 points of data with 10411 aged people ≥ 65 years, were included in the meta-analysis. Mean pooled decayed, missing, and filled teeth among the elderly was 26.84 (26.41-27.28). This index was 26.78 (26.12-27.43) in women and 26.91 (26.32-27.50) in men. Mean number of decayed teeth was 1.48 (1.32-1.65). Mean pooled missing teeth was 24.83 (24.20-25.46), and mean pooled filled teeth was 0.14 (0.12-0.17). The majority (92%) of DMFT was related to missing teeth.

Conclusion

Dental caries has a very high burden on the oral health of the elderly in Iran, mainly responded by tooth extraction.
Employing a Systematic Approach to Biobanking and Analyzing Clinical and Genetic Data for Advancing COVID-19 Research
Authors: Daga Sergio , Fallerini Chiara , Baldassarri Margherita , Fava Francesca , Valentino Floriana , Doddato Gabriella , Benetti Elisa , Furini Simone , Giliberti Annarita , Tita Rossella , Amitrano Sara , Bruttini Mirella , Meloni Ilaria , Pinto Anna Maria , Raimondi Francesco , Stella Alessandra , Biscarini Filippo , Picchiotti Nicola , Gori Marco , Pinoli Pietro , Ceri Stefano , Sanarico Maurizio , Crawley Francis P. ,   GEN-COVID Multicenter Study, Renieri Alessandra , Mari Francesca , Frullanti Elisa
Published: July 2020

Within the GEN-COVID Multicenter Study, biospecimens from more than 1,000 SARS-CoV-2-positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O2 supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical Clustering analysis identified five main clinical categories: i) severe multisystemic failure with either thromboembolic or pancreatic variant; ii) cytokine storm type, either severe with liver involvement or moderate; iii) moderate heart type, either with or without liver damage; iv) moderate multisystemic involvement, either with or without liver damage; v) mild, either with or without hyposmia. GCB and GCPR are further linked to the GEN-COVID Genetic Data Repository (GCGDR), which includes data from Whole Exome Sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population and mapping genetically COVID-19 severity and clinical complexity among patients.
Complement C3 identified as a unique Risk Factor for Disease Severity among Young COVID-19 Patients in Wuhan
Authors: Cheng Weiting , Hornung Roman , Xu Kai , Li Jian
Published: July 2020

Background

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possibly non-linear influences remain unknown.

Methods

Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, collected retrospectively from Jan 24thto Mar 27th, were analyzed. Clinical, demographic, treatment and laboratory data were collected from patients’ medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate and exploit the clinical characteristics of a severe disease course.

Results

A total of 762 young patients (median age 47 years, interquartile ranges [IQR] 38 - 55, range 16 - 60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student’s t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of ASS, CRP and LDH, and decreased lymphocyte counts are influential on disease severity independent of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41-122.3; p=0.039) are particularly associated with the risk for the development of severity specifically in young patients, where no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity.

Conclusion

In young patients with COVID-19, the levels of complement C3 correlated with disease severity and tended to be a good predictor of adverse outcome.
Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome
Authors: Keddie S , Pakpoor J , Mousele C , Pipis M , Machado PM , Foster M , Record CJ , Keh YS , Fehmi J , Paterson RW , Bharambe V , Clayton LM , Allen C , Price O , Wall J , Kiss-Csenki A , Rathnasabapathi DP , Geraldes R , Yermakova T , King-Robson J , Zosmer M , Rajakulendran S , Nortley R , Marshall CR , Newman E , Nirmalananthan N , Kumar G , Pinto AA , Holt J , Lavin TM , Brennan K , Zandi M , Jayaseelan DL , Pritchard J , Hadden RDM , Manji H , Willison HJ , Rinaldi S , Carr AS , Lunn MP
Published: July 2020

Background

Reports of Guillain-Barré Syndrome (GBS) have emerged during the Coronavirus Disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS.

Methods

The epidemiology of GBS cases reported via the UK National Immunoglobulin Database were studied from 2016-2019 and compared to cases reported during the COVID-19 pandemic. For the cohort study, members of the British Peripheral Nerve Society reported all cases of GBS during the pandemic. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases were compared.

Results

The UK GBS incidence from 2016-2019 was 1.65-1.88 per 100,000 people per year. GBS and COVID-19 incidence varied between regions and did not correlate (r = 0.06, 95% CI −0.56 to 0.63, p=0.86). GBS incidence fell between March and May 2020 compared to the same months of 2016-2019. Forty-seven GBS cases were included in the cohort study (13 definite, 12 probable COVID-19 and 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome. Intubation was more frequent in the COVID-19+ve cohort (7/13, 54% vs 5/22, 23% in COVID negative) thought to be related directly to COVID-19 pulmonary involvement.

Conclusions

This study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.
Mathematical modelling of dynamics and containment of COVID-19 in Ukraine
Authors: Kyrychko Yuliya N. , Blyuss Konstantin B. , Brovchenko Igor
Published: July 2020

COVID-19 disease caused by the novel SARS-Cov-2 coronavirus has already brought unprecedented challenges for public health and resulted in huge numbers of cases and deaths worldwide. In the absence of effective vaccine, different countries have employed various other types of non-pharmaceutical interventions to contain the spread of this disease, including quarantines and lockdowns, tracking, tracing and isolation of infected individuals, and social distancing measures. Effectiveness of these and other measures of disease containment and prevention to a large degree depends on good understanding of disease dynamics, and robust mathematical models play an important role for forecasting its future dynamics. In this paper we focus on Ukraine, one of Europe’s largest countries, and develop a mathematical model of COVID-19 dynamics, using latest data on parameters characterising clinical features of disease. For improved accuracy, our model includes age-stratified disease parameters, as well as age- and location-specific contact matrices to represent contacts. We show that the model is able to provide an accurate short-term forecast for the numbers and age distribution of cases and deaths. We also simulated different lockdown scenarios, and the results suggest that reducing work contacts is more efficient at reducing the disease burden than reducing school contacts, or implementing shielding for people over 60.