bluuebunny/crossref_metadata_2025_split huggingface dataset:
S100A8/A9 modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis
Authors: Shankar Madhu , Uwamahoro Nathalie , Holmberg Sandra , Niemiec Maria Joanna , Roth Johannes , Vogl Thomas , Urban Constantin F. 
Published: April 2020

AbstractPeritonitis is a leading cause of severe sepsis in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial, pro-inflammatory protein complex often used as a biomarker for diagnosis of disease activities in many inflammatory disorders. Here we describe the role of S100A8/A9 on inflammatory collateral tissue damage (ICTD).We performed anin vivo Candida albicansdisseminated peritonitis mouse model using WT and S100A9-deficient mice and stimulated primary macrophages with recombinant S100A8/A9 in the presence or absence of the compound paquinimod, a specific inhibitor of S100A9. In addition, the effects on ICTD and fungal clearance were investigated. S100A9-deficient mice developed less ICTD than wildtype mice. Restoration of S100A8/A9 in S100A9 knockout mice resulted in increased ICTD and fungal clearance comparable to wildtype levels. Treatment with paquinimod abolished ICTD.The data indicated that S100A8/A9 controls ICTD levels and host antimicrobial modulation at a systemic level during intra-abdominal candidiasis (IAC).
Classification of COVID-19 in chest X-ray images using DeTraC deep convolutional neural network
Authors: Abbas Asmaa , Abdelsamea Mohammed M. , Medhat Gaber Mohamed 
Published: April 2020

AbstractChest X-ray is the first imaging technique that plays an important role in the diagnosis of COVID-19 disease. Due to the high availability of large-scale annotated image datasets, great success has been achieved using convolutional neural networks (CNNs) for image recognition and classification. However, due to the limited availability of annotated medical images, the classification of medical images remains the biggest challenge in medical diagnosis. Thanks to transfer learning, an effective mechanism that can provide a promising solution by transferring knowledge from generic object recognition tasks to domain-specific tasks. In this paper, we validate and adapt a deepCNN, called Decompose, Transfer, and Compose (DeTraC), for the classification of COVID-19 chest X-ray images.DeTraCcan deal with any irregularities in the image dataset by investigating its class boundaries using a class decomposition mechanism. The experimental results showed the capability ofDeTraCin the detection of COVID-19 cases from a comprehensive image dataset collected from several hospitals around the world. High accuracy of 95.12% (with a sensitivity of 97.91%, and a specificity of 91.87%) was achieved byDeTraCin the detection of COVID-19 X-ray images from normal, and severe acute respiratory syndrome cases.
Demand for hospitalization services for COVID-19 patients in Brazil
Authors: Castro Marcia C. , de Carvalho Lucas Resende , Chin Taylor , Kahn Rebecca , França Giovanny V. A. , Macário Eduardo Marques , de Oliveira Wanderson Kleber 
Published: April 2020

AbstractCOVID-19 is now a pandemic and many of the affected countries face severe shortages of hospital resources. In Brazil, the first case was reported on February 26. As the number of cases grows in the country, there is a concern that the health system may become overwhelmed, resulting in shortages of hospital beds, intensive care unit beds, and mechanical ventilators. The timing of shortage is likely to vary geographically depending on the observed onset and pace of transmission observed, on the availability of resources, and on the actions implemented. Here we consider the daily number of cases reported in municipalities in Brazil to simulate twelve alternative scenarios of the likely timing of shortage, based on parameters consistently reported for China and Italy, on rates of hospital occupancy for other health conditions observed in Brazil in 2019, and on assumptions of allocation of patients in public and private facilities. Results show that hospital services could start to experience shortages of hospital beds, ICU beds, and ventilators in early April, the most critical situation observed for ICU beds. Increasing the allocation of beds for COVID-19 (in lieu of other conditions) or temporarily placing all resources under the administration of the state delays the anticipated start of shortages by a week. This suggests that solutions adopted by the Brazilian government must aim at expanding the available capacity (e.g., makeshift hospitals), and not simply prioritizing the allocation of available resources to COVID-19.
Analytical sensitivity and efficiency comparisons of SARS-COV-2 qRT-PCR primer-probe sets
Authors: Vogels Chantal B.F. , Brito Anderson F. , Wyllie Anne L. , Fauver Joseph R. , Ott Isabel M. , Kalinich Chaney C. , Petrone Mary E. , Casanovas-Massana Arnau , Muenker M. Catherine , Moore Adam J. , Klein Jonathan , Lu Peiwen , Lu-Culligan Alice , Jiang Xiaodong , Kim Daniel J. , Kudo Eriko , Mao Tianyang , Moriyama Miyu , Oh Ji Eun , Park Annsea , Silva Julio , Song Eric , Takahashi Takehiro , Taura Manabu , Tokuyama Maria , Venkataraman Arvind , Weizman Orr-El , Wong Patrick , Yang Yexin , Cheemarla Nagarjuna R. , White Elizabeth B. , Lapidus Sarah , Earnest Rebecca , Geng Bertie , Vijayakumar Pavithra , Odio Camila , Fournier John , Bermejo Santos , Farhadian Shelli , Dela Cruz Charles S. , Iwasaki Akiko , Ko Albert I. , Landry Marie L. , Foxman Ellen F. , Grubaugh Nathan D. 
Published: April 2020

AbstractThe recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays are being used by clinical, research, and public health laboratories. However, it is currently unclear if results from different tests are comparable. Our goal was to evaluate the primer-probe sets used in four common diagnostic assays available on the World Health Organization (WHO) website. To facilitate this effort, we generated RNA transcripts to be used as assay standards and distributed them to other laboratories for internal validation. We then used (1) RNA transcript standards, (2) full-length SARS-CoV-2 RNA, (3) pre-COVID-19 nasopharyngeal swabs, and (4) clinical samples from COVID-19 patients to determine analytical efficiency and sensitivity of the qRT-PCR primer-probe sets. We show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 virus copies per reaction, except for the RdRp-SARSr (Charité) confirmatory primer-probe set which has low sensitivity. Our findings characterize the limitations of currently used primer-probe sets and can assist other laboratories in selecting appropriate assays for the detection of SARS-CoV-2.
Specialisation and plasticity in a primitively social insect
Authors: Patalano S. , Alsina A. , Gregorio-Rodriguez C. , Bachman M. , Dreier S. , Hernando-Herraez I. , Nana P. , Balasubramanian S. , Sumner S. , Reik W. , Rulands S. 
Published: April 2020

AbstractBiological systems not only have the remarkable capacity to build and maintain complex spatio-temporal structures in noisy environments, they can also rapidly break up and rebuild such structures. How such systems can simultaneously achieve both robust specialisation and plasticity is poorly understood. Here we use primitive societies ofPolisteswasps as a model system where we experimentally perturb the social structure by removing the queen and follow the re-establishment of the social steady state over time. We combine a unique experimental strategy correlating time-resolved measurements across vastly different scales with a theoretical approach. We show thatPolistesintegrates antagonistic processes on multiple scales to distinguish between extrinsic and intrinsic perturbations and thereby achieve both robust specialisation and rapid plasticity. The long-term stability of the social structure relies on dynamic DNA methylation which controls transcriptional noise. Such dynamics provide a general principle of how both specialization and plasticity can be achieved in biological systems.One Sentence SummaryA primitive social insect simultaneously achieves specialisation and plasticity by integrating antagonistic dynamics on different scales.HighlightsWe employ a unique experimental approach correlating dynamics of societies, individuals, and epigenetic gene regulationA social insect simultaneously achieves specialisation and plasticity by integrating antagonistic processes on different spatial scalesRegulation of population-level noise by DNA methylation ensures long-term stability of phenotypic specialisation
A way to break bones? The weight of intuitiveness
Authors: Vettese D. , Stavrova T. , Borel A. , Marin J. , Moncel M.-H. , Arzarello M. , Daujeard C. 
Published: April 2020

AbstractDuring the Middle Paleolithic period, bone marrow extraction was an essential source of fat nutrients for hunter-gatherers especially throughout cold and dry seasons. This is attested by the recurrent findings of percussion marks in osteological material from anthropized archaeological levels. Among them some showed indicators that the marrow extraction process was part of a butchery cultural practice, meaning that the inflicted fracturing gestures and techniques were recurrent, standardized and counter-intuitive i.e. culturally influenced. In order to assess the weight of the counter-intuitive factor in the percussion mark pattern distribution, we carried out an experiment that by contrast focuses on the intuitive approach of fracturing bones to extract marrow, involving individual without experience in this activity.We wanted to evaluate the influence of bone morphology and the individuals’ behaviour on the distribution of percussion marks. Twelve experimenters broke 120 limb bones, a series of 10 bones per individual. During the experiment, information concerning the fracture of the bones as well as individual behaviour was collected and was subsequently compared to data from the laboratory study of the remains. Then, we applied an innovative GIS (Geographic Information System) method to analyze the distribution of percussion marks to highlight recurrent patterns. Results show that in spite of all the variables there is a high similarity in the distribution of percussion marks which we consider as intuitive patterns. The factor influenced the distribution for the humerus, radius-ulna and tibia series is the bone morphology, while for the femur series individual behaviour seems to have more weight in the distribution. To go further in the subject we need to compare the intuitive models with the distributions of percussion marks registered in fossil assemblages. Thus, it would be possible to propose new hypotheses on butchering practices based on the results presented in this work.
Experiments on localization accuracy with non-individual and individual HRTFs comparing static and dynamic reproduction methods
Authors: Oberem Josefa , Richter Jan-Gerrit , Setzer Dorothea , Seibold Julia , Koch Iring , Fels Janina 
Published: April 2020

AbstractBinaural reproduction can be used in listening experiments under real-life conditions to achieve a high realism and good reproducibility. In recent years a clear trend to more individual reproduction can be observed as the ability to measure individual head-related-transfer-functions (HRTFs) is becoming more widespread. The question of the accuracy and reproduction methods needed for a realistic playback however has not been sufficiently answered. To evaluate an appropriate approach for binaural reproduction via headphones different head-related-transfer-functions (HRTFs) and reproduction methods were compared in this paper. In a listening test eleven explicitly trained participants were asked to localize eleven sound sources positioned in the right hemisphere using the proximal pointing method. Binaural stimuli based on individually measured HRTFs were compared to those of an artificial head in a static reproduction of stimuli and in three dynamic reproduction methods of different resolutions (5°, 2.5° and 1°). Unsigned errors in azimuth and elevation as well as front-back-confusions and in-head-localization were observed. Dynamic reproduction of any resolution applied turned out fundamental for a reduction of undesired front-back-confusions and in-head-localization. Individually measured HRTFs showed a smaller effect on localization accuracy compared to the influence of dynamic sound reproduction. They were mainly observed to reduce the front-back-confusion rate.
High levels of frataxin overexpression leads to mitochondrial and cardiac toxicity in mouse models
Authors: Belbellaa Brahim , Reutenauer Laurence , Messaddeq Nadia , Monassier Laurent , Puccio Hélène 
Published: April 2020

ABSTRACTFriedreich ataxia (FA) is currently an incurable inherited mitochondrial disease caused by reduced levels of frataxin (FXN). Cardiac dysfunction is the main cause of premature death in FA. AAV-mediated gene therapy constitutes a promising approach for FA, as demonstrated in cardiac and neurological mouse models. While the minimal therapeutic level of FXN protein to be restored and biodistribution have recently been defined for the heart, it is unclear if FXN overexpression could be harmful. Indeed, depending on the vector delivery route and dose administrated, the resulting FXN protein level could reach very high levels in the heart, cerebellum, or in off-target organs such as the liver. The present study demonstrates safety of FXN cardiac overexpression up to 9-fold the normal endogenous level, but significant toxicity to the mitochondria and heart above 20-fold. We show gradual severity with increasing FXN overexpression, ranging from subclinical cardiotoxicity to left ventricle dysfunction. This appears to be driven by impairment of mitochondria respiratory chain, ultrastructure and homeostasis, which lead to myofilaments alteration, cell death and fibrosis. Overall, this study underlines the need, during the development of gene therapy approaches, to consider appropriately vector potency, long term safety and biomarkers to monitor such events.
Brain-wide structural and functional disruption in mice with oligodendrocyte specificNf1deletion is rescued by inhibition of NOS
Authors: Asleh Jad , Shofty Ben , Cohen Nadav , Kavushansky Alexandra , López-Juárez Alejandro , Constantini Shlomi , Ratner Nancy , Kahn Itamar 
Published: April 2020

AbstractNeurofibromin gene (NF1) mutation causes Neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice,Nf1loss in adult oligodendrocyte causes myelin decompaction, and increases oligodendrocyte nitric oxide (NO) levels. Nitric oxide synthase (NOS) inhibitors rescue this pathology. Whether oligodendrocyte pathology is sufficient to affect brainwide structure and account for NF1 imaging findings is unknown. Here, we show thatNf1gene inactivation in adult oligodendrocytes (Plp-Nf1fl/+mice) results in a motor coordination deficit. Magnetic resonance imaging in awake mice shows that fractional anisotropy is reduced in Plp-Nf1fl/+corpus callosum and that interhemispheric functional connectivity in motor cortex is also reduced, consistent with disrupted myelin integrity. Further, NOS-specific inhibition rescued both measures. These results demonstrate that oligodendrocyte defects account for aspects of brain dysfunction in NF1, which can be identified by neuroimaging and ameliorated by NOS inhibition.Significance statementThis study assesses the effects of myelin decompaction on motor behavior and brain-wide structural and functional connectivity, and the effect of nitric oxide synthase (NOS) inhibition by N-nitro-L-arginine methyl ester (L-NAME) on these imaging measures. We report that inducible oligodendrocyte-specific inactivation of theNf1gene, which causes myelin decompaction, results in reduced motor coordination. Using diffusion-based MRI we show reduced myelin integrity and using functional MRI we show reduced functional connectivity in awake passive mice. L-NAME administration results in rescue of the pathology at the mesoscopic level using imaging procedures that can be directly applied to humans to study treatment efficacy in clinical trials.
“A negative feedback loop mediated by the NR4A family of nuclear hormone receptors restrains expansion of B cells that receive signal one in the absence of signal two”
Authors: Tan Corey , Hiwa Ryosuke , Mueller James L. , Vykunta Vivasvan , Hibiya Kenta , Noviski Mark , Huizar John , Brooks Jeremy , Garcia Jose , Heyn Cheryl , Li Zhongmei , Marson Alexander , Zikherman Julie 
Published: April 2020

ABSTRACTAg stimulation (signal 1) triggers B cell activation and proliferation, and primes B cells to recruit, engage, and respond to T cell help (signal 2). However, failure to receive signal 2 within a defined window of time results in an abortive round of proliferation, followed by anergy or apoptosis. Although the molecular basis of T cell help has been extensively dissected, the mechanisms that restrain Ag-stimulated B cells, and enforce dependence upon co-stimulation, are incompletely understood.Nr4a1-3encode a small family of orphan nuclear receptors that are rapidly induced by B cell receptor (BCR) stimulation, yet little is known about their function in humoral immune responses. Here we use germline and conditional loss-of-function mouse models to show thatNr4a1andNr4a3play partially redundant roles to restrain both the survival and proliferation of B cells that receive signal 1 in the absence of co-stimulatory signals, and do so in part by repressing expression of BATF and consequently c-MYC. Correspondingly, Ab responses to TI-2 immunogens are enhanced in the absence ofNr4a1, but are unaltered in response to immunogens that incorporate co-stimulatory signals. Unexpectedly, we also identify a role for the NR4A family in restraining B cell access to T cell help by repressing expression of the T cell chemokines CCL3/4, as well as CD86 and ICAM1, and show that this is relevant under conditions of competition for limiting T cell help. Our studies collectively reveal a novel negative feedback loop mediated by the NR4A family that increases B cell dependence upon T cell help and restrains strongly Ag-activated B cell clones from monopolizing limiting amounts of T cell help. We speculate that this imposes B cell tolerance and dampens immunodominance to facilitate preservation of clonal diversity during an immune response.
A Mendelian randomization study of glycemic and anthropometric traits and Parkinson’s disease
Authors: Grover Sandeep , Graf Ricarda , Klein Christine , Brüggemann Norbert , König Inke R. , Greco M Fabiola Del , Sharma Manu 
Published: April 2020

AbstractBackgroundImpaired glucose and obesity are frequently observed in patients with Parkinson’s disease (PD), although it is unclear whether the impairment precedes or results from the neurodegeneration.ObjectiveWe aimed to assess whether glycemic and anthropometric traits can influence the risk of PD in 33,674 cases and 449,056 healthy controls using the Mendelian randomization (MR) framework.MethodsWe investigated causality with a two-sample MR approach in the European population to compute effect estimates with summary statistics from available discovery meta-analyses of genome-wide association studies (GWAS) on glycemic and anthropometric traits.ResultsWe considered a threshold of p-value=0.0038 as significant after accounting for multiple testing, and p-value<0.05 was considered to be a suggestive evidence for a potential association. We observed a protective effect of waist-hip ratio (WHR) on PD (Inverse variance-weighted (IVW): ORIVW=0.735; 95%CI= 0.622–0.868; p-value=0.0003; I2index=22.0%; MR-Egger intercept p-value=0.1508; Cochran Q test p-value=0.0003). The association was further retained after the exclusion of overlapping UK biobank (UKB) samples between the WHR and PD datasets (ORIVW=0.791; 95%CI=0.659–0.950; p-value=0.012; I2index=13.0%; MR-Egger intercept p-value=0.733; Cochran Q test p-value=0.035). The sensitivity analysis provided suggestive evidence of an increased risk of PD on fasting glucose (FG) (βIVW=0.0188; 95%CI=0.0062–0.0313, p-value=0.0055; I2index=0.0%; MR-Egger intercept p-value=0.0957; Cochran Q test p-value=0.4555) and protective effect of PD on T2D (Weighted median effect: ORWME=0.946; 95%CI=0.9290.983; p-value=0.0051; Weighted mode effect: ORMBE=0.943; 95%CI=0.904–0.983; p-value=0.0116).ConclusionsOur results showed that central or abdominal obesity may be protective against PD development, independent of glucose levels.
mtDNAcombine: tools to combine sequences from multiple studies
Authors: Miller Eleanor F. , Manica Andrea 
Published: April 2020

AbstractToday an unprecedented amount of genetic sequence data is stored in publicly available repositories. For decades now, mitochondrial DNA (mtDNA) has been the workhorse of genetic studies, and as a result, there is a large volume of mtDNA data available in these repositories for a wide range of species. Indeed, whilst whole genome sequencing is an exciting prospect for the future, for most non-model organisms’ classical markers such as mtDNA remain widely used. By compiling existing data from multiple original studies, it is possible to build powerful new datasets capable of exploring many questions in ecology, evolution and conservation biology. One key question that these data can help inform is what happened in a species’ demographic past. However, compiling data in this manner is not trivial, there are many complexities associated with data extraction, data quality and data handling. Here we present the mtDNAcombine package, a collection of tools developed to manage some of the major decisions associated with handling multi-study sequence data with a particular focus on preparing mtDNA data for Bayesian Skyline Plot demographic reconstructions.