bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adapting the UK Biobank brain imaging protocol and analysis pipeline for the C-MORE multi-organ study of COVID-19 survivors
Authors: Griffanti Ludovica , Raman Betty , Alfaro-Almagro Fidel , Filippini Nicola , Cassar Mark Philip , Sheerin Fintan , Okell Thomas W , McConnell Flora A Kennedy , Chappell Michael A , Wang Chaoyue , Arthofer Christoph , Lange Frederik J , Andersson Jesper , Mackay Clare E , Tunnicliffe Elizabeth , Rowland Matthew , Neubauer Stefan , Miller Karla L , Jezzard Peter , Smith Stephen M 
Published: May 2021

ABSTRACTSARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study.The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 minutes. The automated imaging pipeline derives 1575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, these quantitative measures were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed that recovered COVID-19 patients had a decrease in frontal grey matter volumes, an increased burden of white matter hyperintensities, and reduced mean diffusivity in the total and normal appearing white matter in the posterior thalamic radiation and sagittal stratum, relative to controls. These differences were generally more prominent in patients who received organ support. Increased T2* in the thalamus was also observed in recovered COVID-19 patients, with a more prominent increase for non-critical patients.This initial evidence of brain changes in COVID-19 survivors prompts the need for further investigations. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in large-scale studies. The pipeline is widely applicable and will contribute to new analyses to hopefully clarify the medium to long-term effects of COVID-19.HighlightsUK Biobank brain MRI protocol and pipeline was adapted for multiorgan MRI of COVID-19High-quality brain MRI data from 5 modalities are acquired in 17 minutesAnalysis pipeline derives 1575 IDPs of brain anatomy, perfusion, and microstructureEvidence of brain changes in COVID-19 survivors was found in the C-MORE studyThis MRI protocol is now being used in multiple large-scale studies on COVID-19
Decoding accelerometry for classification and prediction of critically ill patients with severe brain injury
Authors: Bhattacharyay Shubhayu , Rattray John , Wang Matthew , Dziedzic Peter H. , Calvillo Eusebia , Kim Han B. , Joshi Eshan , Kudela Pawel , Etienne-Cummings Ralph , Stevens Robert D. 
Published: May 2021

ABSTRACTOur goal is to explore quantitative motor features in critically ill patients with severe brain injury (SBI). We hypothesized that computational decoding of these features would yield information on underlying neurological states and outcomes. Using wearable microsensors placed on all extremities, we recorded a median 24.1 (IQR: 22.8–25.1) hours of high-frequency accelerometry data per patient from a prospective cohort (n= 69) admitted to the ICU with SBI. Models were trained using time-, frequency-, and wavelet-domain features and levels of responsiveness and outcome as labels. The two primary tasks were detection of levels of responsiveness, assessed by motor sub-score of the Glasgow Coma Scale (GCSm), and prediction of functional outcome at discharge, measured with the Glasgow Outcome Scale–Extended (GOSE). Detection models achieved significant (AUC: 0.70 [95% CI: 0.53–0.85]) and consistent (observation windows: 12 min – 9 hours) discrimination of SBI patients capable of purposeful movement (GCSm > 4). Prediction models accurately discriminated patients of upper moderate disability or better (GOSE > 5) with 2–6 hours of observation (AUC: 0.82 [95% CI: 0.75–0.90]). Results suggest that time series analysis of motor activity yields clinically relevant insights on underlying functional states and short-term outcomes in patients with SBI.
Modelling the effect of a border closure between Switzerland and Italy on the spatiotemporal spread of COVID-19 in Switzerland
Authors: Grimée Mathilde , Dunbar Maria Bekker-Nielsen , Hofmann Felix , Held Leonhard 
Published: May 2021

AbstractWe present an approach to extend the Endemic-Epidemic (EE) modelling framework for the analysis of infectious disease data. In its spatiotemporal application, spatial dependencies have originally been captured by a power law applied to static neighbourhood matrices. We propose to adjust these weight matrices over time to reflect changes in spatial connectivity between geographical units. We illustrate this extension by modelling the spread of coronavirus disease 2019 (COVID-19) between Swiss and bordering Italian regions in the first wave of the COVID-19 pandemic. We adjust the spatial weights with data describing the daily changes in population mobility patterns, and indicators of border closures describing the state of travel restrictions since the beginning of the pandemic. We use these time-dependent weights to fit an EE model to the region-stratified time series of new COVID-19 cases. We then adjust the weight matrices to reflect two counterfactual scenarios of border closures and draw counterfactual predictions based on these, to retrospectively assess the usefulness of border closures. We observed that predictions based on a scenario where no closure of the Swiss-Italian border occurred increased the number of cumulative cases in Switzerland by a factor of 2.5 over the study period. Conversely, a closure of the Swiss-Italian border two weeks earlier than implemented would have resulted in only a 12% decrease in the number of cases and merely delayed the epidemic spread by a couple weeks. Despite limitations in the current study, we believe it provides useful insight into modelling the effect of epidemic countermeasures on the spatiotemporal spread of COVID-19.
Silica-encapsulated DNA tracers for measuring aerosol distribution dynamics in real-world settings
Authors: Luescher Anne M. , Koch Julian , Stark Wendelin J. , Grass Robert N. 
Published: May 2021

ABSTRACTAerosolized particles play a significant role in human health and environmental risk management. The global importance of aerosol-related hazards, such as the circulation of pathogens and high levels of air pollutants, have led to a surging demand for suitable surrogate tracers to investigate the complex dynamics of airborne particles in real-world scenarios. In this study, we propose a novel approach using silica particles with encapsulated DNA (SPED) as a tracing agent for measuring aerosol distribution indoors. In a series of experiments with a portable setup, SPED were successfully aerosolized, re-captured and quantified using quantitative polymerase chain reaction (qPCR). Position-dependency and ventilation effects within a confined space could be shown in a quantitative fashion achieving detection limits below 0.1 ng particles per m3 of sampled air. In conclusion, SPED show promise for a flexible, cost-effective and low-impact characterization of aerosol dynamics in a wide range of settings.PRACTICAL IMPLICATIONSFor the first time, silica particles with encapsulated DNA were used to characterize a confined indoor space regarding position- and ventilation-dependent effects of aerosol distribution. The method described here introduces SPED as a novel, non-toxic, low-impact, cost-effective and easy-to-use aerosol tracing platform that can be used to examine real-world environments. The mobile setup presented here as a proof of concept shows that SPED can be aerosolized and re-captured, followed by highly sensitive quantitative barcode-specific PCR analysis. The results revealed that this tracing method can detect position-dependent differences in exposure and ventilation effects influencing distribution dynamics. In the future, SPED could be engineered to exhibit custom-designed properties and be employed within a wide range of setups and high-capacity multi-tracing combinations.
CovidMulti-Net: A Parallel-Dilated Multi Scale Feature Fusion Architecture for the Identification of COVID-19 Cases from Chest X-ray Images
Authors: Islam Khan Md. Saikat , Rahman Anichur , Karim Md. Razaul , Bithi Nasima Islam , Band Shahab S. , Dehzangi Abdollah , Alinejad-Rokny Hamid 
Published: May 2021

AbstractThe COVID-19 pandemic is an emerging respiratory infectious disease, having a significant impact on the health and life of many people around the world. Therefore, early identification of COVID-19 patients is the fastest way to restrain the spread of the pandemic. However, as the number of cases grows at an alarming pace, most developing countries are now facing a shortage of medical resources and testing kits. Besides, using testing kits to detect COVID-19 cases is a time-consuming, expensive, and cumbersome procedure. Faced with these obstacles, most physicians, researchers, and engineers have advocated for the advancement of computer-aided deep learning models to assist healthcare professionals in quickly and inexpensively recognize COVID-19 cases from chest X-ray (CXR) images. With this motivation, this paper proposes a “CovidMulti-Net” architecture based on the transfer learning concept to classify COVID-19 cases from normal and other pneumonia cases using three publicly available datasets that include 1341, 1341, and 446 CXR images from healthy samples and 902, 1564, and 1193 CXR images infected with Viral Pneumonia, Bacterial Pneumonia, and COVID-19 diseases. In the proposed framework, features from CXR images are extracted using three well-known pre-trained models, including DenseNet-169, ResNet-50, and VGG-19. The extracted features are then fed into a concatenate layer, making a robust hybrid model. The proposed framework achieved a classification accuracy of 99.4%, 95.2%, and 94.8% for 2-Class, 3-Class, and 4-Class datasets, exceeding all the other state-of-the-art models. These results suggest that the “CovidMulti-Net” framework’s ability to discriminate individuals with COVID-19 infection from healthy ones and provides the opportunity to be used as a diagnostic model in clinics and hospitals. We also made all the materials publicly accessible for the research community at:https://github.com/saikat15010/CovidMulti-Net-Architecture.git.
Analysis of the Second COVID-19 Wave in India Using a Birth-Death Model
Authors: Viswanath Narayanan C. 
Published: May 2021

AbstractIndia is witnessing the second wave of the COVID-19 disease from the first half of February 2021. The method in [5] is applied here to analyze the second wave in India. We start with fitting a birth-death model to the active and total cases data for the period from 13th to 28th February 2021. This initial dataset is expanded step by step by adding the two future week’s data to it until 14th May 2021. This resulted in six models in total. The efficacy of each model is tested in terms of predictions made for the next two weeks. The infectivity rates are found to be ever-increasing in the case of the five initial models. The infectivity rate for the sixth model, which is based on the data from 13th February to 14th May 2021, shows a decreasing nature with an increase in time. This indicates a decline in the second wave, which may start from 4th June 2021 according to the fitted parameters.
External Cues Improve Visual Working Memory Encoding in the Presence of Salient Distractors in Schizophrenia
Authors: Barnes-Scheufler Catherine V. , Rösler Lara , Schaum Michael , Schiweck Carmen , Peters Benjamin , Mayer Jutta S. , Reif Andreas , Wibral Michael , Bittner Robert A. 
Published: May 2021

ABSTRACTBackgroundPeople with schizophrenia (PSZ) are impaired in attentional prioritization of non-salient but relevant stimuli over salient distractors during visual working memory (VWM) encoding. Conversely, guidance of top-down attention by external predictive cues is intact. Yet, it is unknown whether this preserved ability can help PSZ encode more information in the presence of salient distractors.MethodsWe employed a visuospatial change-detection task using four Gabor patches with differing orientations in 66 PSZ and 74 healthy controls (HCS). Two Gabor patches flickered which were designated either as targets or distractors and either a predictive or a non-predictive cue was displayed to manipulate top-down attention, resulting in four conditions.ResultsWe observed significant effects of group, salience and cue as well as significant interactions of salience by cue, group by salience and group by cue. Across all conditions, PSZ stored significantly less information in VWM than HCS. PSZ stored significantly less non-flickering than flickering information with a non-predictive cue. However, PSZ stored significantly more flickering and non-flickering information with a predictive cue.ConclusionsOur findings indicate that control of attentional selection is impaired in schizophrenia. We demonstrate that additional top-down information significantly improves performance in PSZ. The observed deficit in attentional control suggests a disturbance of GABAergic inhibition in early visual areas. Moreover, our findings are indicative of a mechanism for enhancing attentional control in PSZ, which could be utilized by pro-cognitive interventions. Thus, the current paradigm is suitable to reveal both preserved and compromised cognitive component processes in schizophrenia.
Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway
Authors: Garcia Ignacio , Orellana-Muñoz Sara , Ramos-Alonso Lucía , Andersen Aram N. , Zimmermann Christine , Eriksson Jens , Bøe Stig Ove , Kaferle Petra , Papamichos-Chronakis Manolis , Chymkowitch Pierre , Enserink Jorrit M. 
Published: May 2021

SummaryMechanisms have evolved that allow cells to detect signals and generate an appropriate response. The accuracy of these responses relies on the ability of cells to discriminate between signal and noise. How cells filter noise in signaling pathways is not well understood. Here, we analyze noise suppression in the yeast pheromone signaling pathway and show that the poorly characterized protein Kel1 serves as a major noise suppressor and prevents cell death. At the molecular level, Kel1 prevents spontaneous activation of the pheromone response by inhibiting membrane recruitment of Ste5 and Far1. Only a hypophosphorylated form of Kel1 suppresses signaling, reduces noise and prevents pheromone-associated cell death, and our data indicate that the MAPK Fus3 contributes to Kel1 phosphorylation. Taken together, Kel1 serves as a phospho-regulated suppressor of the pheromone pathway to reduce noise, inhibit spontaneous activation of the pathway, regulate mating efficiency, and to prevent pheromone-associated cell death.
Cortical Representations of Concrete and Abstract Concepts in Language Combine Visual and Linguistic Representations
Authors: Tang Jerry , LeBel Amanda , Huth Alexander G. 
Published: May 2021

AbstractThe human semantic system stores knowledge acquired through both perception and language. To study how semantic representations in cortex integrate perceptual and linguistic information, we created semantic word embedding spaces that combine models of visual and linguistic processing. We then used these visually-grounded semantic spaces to fit voxelwise encoding models to fMRI data collected while subjects listened to hours of narrative stories. We found that cortical regions near the visual system represent concepts by combining visual and linguistic information, while regions near the language system represent concepts using mostly linguistic information. Assessing individual representations near visual cortex, we found that more concrete concepts contain more visual information, while even abstract concepts contain some amount of visual information from associated concrete concepts. Finally we found that these visual grounding effects are localized near visual cortex, suggesting that semantic representations specifically reflect the modality of adjacent perceptual systems. Our results provide a computational account of how visual and linguistic information are combined to represent concrete and abstract concepts across cortex.
c-di-AMP is essential for the virulence of Enterococcus faecalis
Authors: Kundra Shivani , Lam Ling Ning , Kajfasz Jessica K. , Casella Leila G. , Andersen Marissa J. , Abranches Jacqueline , Flores-Mireles Ana L. , Lemos José A. 
Published: May 2021

ABSTRACTSecond messenger nucleotides are produced by bacteria in response to environmental stimuli and play a major role in the regulation of processes associated with bacterial fitness, including but not limited to osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. In this study, we uncovered the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis by isolating and characterizing strains lacking genes responsible for c-di-AMP synthesis (cdaA) and degradation (dhhP and gdpP). Using complementary approaches, we demonstrated that either complete loss of c-di-AMP (ΔcdaA strain) or c-di-AMP accumulation (ΔdhhP, ΔgdpP and ΔdhhPΔgdpP strains) drastically impaired general cell fitness and virulence of E. faecalis. In particular, the ΔcdaA strain was highly sensitive to envelope-targeting antibiotics, was unable to multiply and quickly lost viability in human serum or urine ex vivo, and was avirulent in an invertebrate (Galleria mellonella) and in two catheter-associated mouse infection models that recapitulate key aspects of enterococcal infections in humans. In addition to evidence linking these phenotypes to altered activity of metabolite and peptide transporters and inability to maintain osmobalance, we found that the attenuated virulence of ΔcdaA could be also attributed to a defect in Ebp pilus production and activity that severely impaired biofilm formation under both in vitro and in vivo conditions. Collectively, these results reveal that c-di-AMP signaling is essential for E. faecalis pathogenesis and a desirable target for drug development.IMPORTANCEEnterococcus faecalis is an opportunistic pathogen and leading cause of multidrug resistant hospital-acquired infections. During the course of an infection, bacteria encounter multiple adverse (stress) conditions and understanding the adaptive mechanisms used by pathogens to survive these stresses can facilitate the development of new antimicrobial therapies. Here, we used in vitro, ex vivo and in vivo approaches to determine the importance of the second messenger nucleotide c-di-AMP, a global regulator essential for bacterial adaptation to osmotic stress, to E. faecalis pathophysiology. We demonstrated that either accumulation of c-di-AMP or complete loss of c-di-AMP impaired cell fitness and virulence of E. faecalis. Remarkably, the strain that was unable to produce c-di-AMP was avirulent in three animal infection models indicating that c-di-AMP signaling is essential for E. faecalis pathogenesis and a suitable antimicrobial target.
Epi-mutations for spermatogenic defects by maternal exposure to Di (2-ethylhexyl) phthalate
Authors: Tando Yukiko , Hiura Hitoshi , Takehara Asuka , Ito-Matsuoka Yumi , Arima Takahiro , Matsui Yasuhisa 
Published: May 2021

AbstractExposure to environmental factors during fetal development may lead to epigenomic modifications in fetal germ cells, altering gene expression and promoting diseases in successive generations. In mouse, maternal exposure to Di (2-ethylhexyl) phthalate (DEHP) is known to induce defects in spermatogenesis in successive generations, but the mechanism(s) of impaired spermatogenesis are unclear. Here, we showed that maternal DEHP exposure results in DNA hypermethylation of promoters of spermatogenesis-related genes in fetal testicular germ cells in F1 mice, and hypermethylation ofHist1h2ba, Sycp1andTaf7l,which are crucial for spermatogenesis, persisted from fetal testicular cells to adult spermatogonia, resulting in the downregulation of expression of these genes. Forced methylation of these gene promoters silenced expression of these loci in a reporter assay. Expression and methylation of those genes tended to be downregulated and increased, respectively in F2 spermatogonia following maternal DEHP exposure. These results suggested that DEHP-induced hypermethylation ofHist1h2ba, Sycp1andTaf7lin fetal germ cells results in downregulation of these genes in spermatogonia and subsequent defects in spermatogenesis, at least in the F1 generation.
Lung mesenchymal cell diversity rapidly increases at birth and is profoundly altered by hyperoxia
Authors: Zanini Fabio , Che Xibing , Suresh Nina E , Knutsen Carsten , Klavina Paula , Xie Yike , Domingo-Gonzalez Racquel , Liu Min , Jones Robert C , Quake Stephen R , Alvira Cristina M. , Cornfield David N. 
Published: May 2021

AbstractLung mesenchymal cells play an essential role in development and at birth, as the lung moves from a fluid-filled to an oxygen-rich environment with a stable gas-liquid interface. The molecular details and cellular changes accompanying this highly coordinated process remain incompletely understood. Therefore, we performed single cell transcriptomics and in-situ imaging of the developing lung in both health and disease to characterize the spectrum of mesenchymal cell states prior to the onset of air-breathing life through late alveolarization to gain insight into their role in orchestrating tissue maturation. We found that cell type diversity in the mesenchymal compartment increases rapidly during normal development but is delayed during neonatal exposure to 80% O2hyperoxia, a model for bronchopulmonary dysplasia. This study identifies the molecular transitions between populations of mesenchymal cells at discrete developmental time points across fibroblast, smooth muscle, and mural compartments and elucidates the global and cell type-specific effects of neonatal hyperoxia, including the emergence ofActa1+ cells which are absent in normoxic neonatal lungs. These granular insights hold the promise of targeted treatment for neonatal lung disease, which remains a major cause of infant morbidity and mortality across the world.
Hif1α is required for Wnt regulated gene expression during Xenopus tropicalis tail regeneration
Authors: Patel Jeet H. , Schattinger Preston A. , Takayoshi Evan E. , Wills Andrea E. 
Published: May 2021

AbstractRegeneration of complex tissues is initiated by an injury-induced stress response, eventually leading to activation of developmental signaling pathways such as Wnt signaling. How early injury cues are interpreted and coupled to activation of these developmental signals and their targets is not well understood. Here, we show that Hif1α, a stress induced transcription factor, is required for tail regeneration in Xenopus tropicalis. We find that Hif1α is required for regeneration of differentiated axial tissues, including axons and muscle. Using RNA-sequencing, we find that Hif1α and Wnt converge on a broad set of genes required for posterior specification and differentiation, including the posterior hox genes. We further show that Hif1α is required for transcription via a Wnt-responsive element, a function that is conserved in both regeneration and early neural patterning. Our findings indicate a regulatory role for Hif1α in Wnt mediated gene expression across multiple tissue contexts.