bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions and behavioural responses of the general public during the COVID-19 pandemic: A cross-sectional survey of UK Adults
Authors: Atchison Christina J , Bowman Leigh , Vrinten Charlotte , Redd Rozlyn , Pristerà Philippa , Eaton Jeffrey W , Ward Helen 
Published: April 2020

ABSTRACTObjectiveTo examine risk perceptions and behavioural responses of the UK adult population during the early phase of the COVID-19 epidemic in the UK.DesignA cross-sectional surveySettingConducted with a nationally representative sample of UK adults within 48 hours of the UK Government advising the public to stop non-essential contact with others and all unnecessary travel.Participants2,108 adults living in the UK aged 18 years and over. Data were collected between March 17 and 18 2020.Main outcome measuresDescriptive statistics for all survey questions, including the number of respondents and the weighted percentages. Logistic regression was used to identify sociodemographic variation in: (1) adoption of social-distancing measures, (2) ability to work from home, and (3) willingness and (4) ability to self-isolate.ResultsOverall, 1,992 (94.2%) respondents reported taking at least one preventive measure: 85.8% washed their hands with soap more frequently; 56.5% avoided crowded areas and 54.5% avoided social events. Adoption of social-distancing measures was higher in those aged over 70 compared to younger adults aged 18 to 34 years (aOR:1.9; 95% CI:1.1 to 3.4). Those with the lowest household income were six times less likely to be able to work from home (aOR:0.16; 95% CI:0.09 to 0.26) and three times less likely to be able to self-isolate (aOR:0.31; 95% CI:0.16 to 0.58). Ability to self-isolate was also lower in black and minority ethnic groups (aOR:0.47; 95% CI:0.27 to 0.82). Willingness to self-isolate was high across all respondents.ConclusionsThe ability to adopt and comply with certain NPIs is lower in the most economically disadvantaged in society. Governments must implement appropriate social and economic policies to mitigate this. By incorporating these differences in NPIs among socio-economic subpopulations into mathematical models of COVID-19 transmission dynamics, our modelling of epidemic outcomes and response to COVID-19 can be improved.
Evaluation of the Anticipated Burden of COVID-19 on Hospital-Based Healthcare Services Across the United States
Authors: Khera Rohan , Jain Snigdha , Lin Zhenqiu , Ross Joseph S. , Krumholz Harlan M 
Published: April 2020

BackgroundCoronavirus disease-19 (COVID-19) is a global pandemic, with the potential to infect nearly 60% of the population. The anticipated spread of the virus requires an urgent appraisal of the capacity of US healthcare services and the identification of states most vulnerable to exceeding their capacityMethodsIn the American Hospital Association survey for 2018, a database of US community hospitals, we identified total inpatient beds, adult intensive care unit (ICU) beds, and airborne isolation rooms across all hospitals in each state of continental US. The burden of COVID-19 hospitalizations was estimated based on a median hospitalization duration of 12 days and was evaluated for a 30-day reporting period.ResultsAt 5155 US community hospitals across 48 states in the contiguous US and Washington DC, there were a total of 788,032 inpatient beds, 68,280 adult ICU beds, and 44,222 isolation rooms. The median daily bed occupancy was 62.8% (IQR 58.1%, 66.6%) across states. Nationally, for every 10,000 individuals, there are 24.2 inpatient beds, 2.8 adult ICU beds, and 1.4 isolation beds. There is a 3-fold variation in the number of inpatient beds available across the US, ranging from 16.4 per 10,000 in Oregon to 47 per 10,000 in South Dakota. There was also a similar 3-fold variation in available or non-occupied beds, ranging from 4.7 per 10,000 in Connecticut through 18.3 per 10,000 in North Dakota. The availability of ICU beds is low nationally, ranging from 1.4 per 10,000 in Nevada to 4.7 per 10000 in Washington DC.Hospitalizations for COVID-19 in a median 0.2% (IQR 0.2 %, 0.3%) of state population, or 1.4% of state’s older adults (1.0%, 1.9%) will require all non-occupied beds. Further, a median 0.6% (0.5%, 0.8%) of state population, or 3.9% (3.1%, 4.6%) of older individuals would require 100% of inpatient beds.ConclusionThe COVID-19 pandemic is likely to overwhelm the limited number of inpatient and ICU beds for the US population. Hospitals in half of US states would exceed capacity if less than 0.2% of the state population requires hospitalization in any given month.
Mechanical characteristics of ultrafast zebrafish larval swimming muscles
Authors: Mead A. F. , Kennedy G. G. , Palmer B. M. , Ebert A. M. , Warshaw D. M. 
Published: April 2020

AbstractZebrafish (Danio rerio) swim within days of fertilization, powered by muscles of the axial myotomes. Forces generated by these muscles can be measured rapidly in whole, intact larval tails by adapting protocols developed forex vivomuscle mechanics. But it is not known how well these measurements reflect the function of the underlying muscle fibers and sarcomeres. Here we consider the anatomy of the 5-day-old, wild-type larval tail, and implement technical modifications to measuring muscle physiology in intact tails. Specifically, we quantify fundamental relationships between force, length, and shortening velocity, and capture the extreme contractile speeds required to swim with tail-beat frequencies of 80-100 Hz. Therefore, we analyze 1000 frames/second movies to track the movement of structures, visible in the transparent tail, which correlate with sarcomere length. We also characterize the passive viscoelastic properties of the preparation to isolate forces contributed by non-muscle structures within the tail. Myotomal muscles generate more than 95% of their maximum isometric stress (76±3 mN/mm2) over the range of muscle lengths usedin vivo. They have rapid twitch kinetics (full width at half-maximum stress: 11±1 msec) and a high twitch to tetanus ratio (0.91±0.05), indicating adaptations for fast excitation-contraction coupling. Although contractile stress is relatively low, myotomal muscles develop high net power (134±20 W/kg at 80 Hz) in cyclical work loop experiments designed to simulate thein vivodynamics of muscle fibers during swimming. When shortening at a constant speed of 7±1 muscle lengths/second, muscles develop 86±2% of isometric stress, while peak instantaneous power during 100Hz work loops occurs at 18±2 muscle lengths/second. These approaches can improve the usefulness of zebrafish as a model system for muscle research by providing a rapid and sensitive functional readout for experimental interventions.Statement of significanceThe zebrafish (Danio rerio) may prove a uniquely efficient model system for characterizing vertebrate muscle physiology. Transparent, drug-permeable larva – each, in essence, a fully functional muscle – can be generated rapidly, inexpensively, and in large numbers. Critically, the zebrafish genome contains homologs of major muscle genes and is highly amenable to manipulation. To reach its potential, reliable (and preferably rapid) means are needed to observe the effects of experimental interventions on larval muscle function. In the present study we show how mechanical measurements made on whole, intact larval tails can provide a readout of fundamental muscle-mechanical properties. Additionally, we show that these muscles are among the fastest ever measured, and therefore worthy of study in their own right.
Diffusion Basis Spectrum Imaging with Deep Neural Network Differentiates Distinct Histology in Pediatric Brain Tumors
Authors: Ye Zezhong , Srinivasa Komal , Lin Joshua , Viox Jeffrey D. , Song Chunyu , Wu Anthony T. , Sun Peng , Song Sheng-Kwei , Dahiya Sonika , Rubin Joshua B. 
Published: April 2020

AbstractHigh-grade pediatric brain tumors constitute the highest mortality of cancer-death in children. While conventional MRI has been widely adopted for examining pediatric high-grade brain tumor clinically, accurate neuroimaging detection and differentiation of tumor histopathology for improved diagnosis, surgical planning, and treatment evaluation, remains an unmet need in the clinical management of pediatric brain tumor. We employed a novel Diffusion Histology Imaging (DHI) approach that incorporates diffusion basis spectrum imaging (DBSI) and deep neural network. DHI aims to detect, differentiate, and quantify heterogenous areas in pediatric high-grade brain tumors, which include normal white matter (WM), densely cellular tumor (DC tumor), less densely cellular tumor (LDC tumor), infiltrating edge, necrosis, and hemorrhage. Distinct diffusion metric combination would thus indicate the unique distributions of each distinct tumor histology features. DHI, by incorporating DBSI metrics and the deep neural network algorithm, classified pediatric tumor histology with an overall accuracy of 83.3%. Receiver operating analysis (ROC) analysis suggested DHI’s great capability in distinguishing individual tumor histology with AUC values (95%CI) of 0.983 (0.985-0.989), 0.961 (0.957-0.964), 0.993 (0.992-0.994), 0.953 (0.947-0.958), 0.974 (0.970-0.978) and 0.980 (0.977-0.983) for normal WM, DC tumor, LDC tumor, infiltrating edge, necrosis and hemorrhage, respectively. Our results suggest that DBSI-DNN, or DHI, accurately characterized and classified multiple tumor histologic features in pediatric high-grade brain tumors. If further validated in patients, the novel DHI might emerge as a favorable alternative to the current neuroimaging techniques to better guide biopsy and resection as well as monitor therapeutic response in patients with high-grade brain tumors.
Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis (ALS)
Authors: Steyn Frederik J. , Kirk Siobhan E. , Tefera Tesfaye W. , Xie Teresa Y. , Tracey Timothy J. , Kelk Dean , Wimberger Elyse , Garton Fleur C. , Roberts Llion , Chapman Sarah , Coombes Jeff S. , Leevy W. Matthew , Ferri Alberto , Valle Cristiana , René Frédérique , Loeffler Jean-Philippe , McCombe Pamela A. , Henderson Robert D. , Ngo Shyuan T. 
Published: April 2020

AbstractAmyotrophic lateral sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons, yet an increasing number of studies in both mouse models and patients with ALS suggest that altered metabolic homeostasis is a feature of disease. Pre-clinical and clinical studies have shown that modulation of energy balance can be beneficial in ALS. However, our capacity to target specific metabolic pathways or mechanisms requires detailed understanding of metabolic dysregulation in ALS. Here, using the SOD1G93Amouse model of ALS, we demonstrate that an increase in whole-body metabolism occurs at a time when glycolytic muscle exhibits an increased dependence on fatty acid oxidation. Using myotubes derived from muscle of ALS patients, we also show that increased dependence on fatty acid oxidation is associated with increased whole-body energy expenditure. In the present study, increased fatty acid oxidation was associated with slower disease progression. However, we observed considerable heterogeneity in whole-body metabolism and fuel oxidation profiles across our patient cohort. Thus, future studies that decipher specific metabolic changes at an individual patient level are essential for the development of treatments that aim to target metabolic pathways in ALS.
CLUE: a bioinformatic and wet-lab pipeline for multiplexed cloning of custom sgRNA libraries
Authors: Becker Martin , Noll-Puchta Heidi , Amend Diana , Nolte Florian , Fuchs Christiane , Jeremias Irmela , Braun Christian J 
Published: April 2020

AbstractThe systematic perturbation of genomes using CRISPR/Cas9 deciphers gene function at an unprecedented rate, depth and ease. Commercially available sgRNA libraries typically contain tens of thousands of pre-defined constructs, resulting in a complexity challenging to handle. In contrast, custom sgRNA libraries comprise gene sets of self-defined content and size, facilitating experiments under complex conditions such asin vivosystems. To streamline and upscale cloning of custom libraries, we present CLUE, a bioinformatic and wet-lab pipeline for the multiplexed generation of pooled sgRNA libraries. CLUE starts from lists of genes or pasted sequences provided by the user and designs a single synthetic oligonucleotide pool containing various libraries. At the core of the approach, a barcoding strategy for unique primer binding sites allows amplifying different distinct libraries from one single oligonucleotide pool. We prove the approach to be straightforward, versatile and specific, yielding uniform sgRNA distributions in all resulting libraries, virtually devoid of cross-contaminations. Forin silicolibrary multiplexing and design, we established an easy-to-use online platform atwww.crispr-clue.de. All in all, CLUE represents a resource-saving approach to produce numerous high quality custom sgRNA libraries in parallel, which will foster their broad use across molecular biosciences.
Expansion of frozen hybrids in the guppy ectoparasite,Gyrodactylus turnbulli
Authors: Konczal Mateusz , Przesmycka Karolina J. , Mohammed Ryan S. , Hahn Christoph , Cable Jo , Radwan Jacek 
Published: April 2020

AbstractHybridization is one of the major factors contributing to the emergence of highly successful parasites. Hybrid vigor can play an important role in this process, but subsequent rounds of recombination in the hybrid population may dilute its effects. Increased fitness of hybrids can, however, be frozen by asexual reproduction. Here, we identify invasion of a “frozen hybrid” genotype in natural populations ofGyrodactylus turnbulli, a facultatively sexual ectoparasitic flatworm that causes significant damage to its fish host. We re-sequenced genomes of these parasites infecting guppies from six Trinidad and Tobago populations, and found surprisingly high discrepancy in genome-wide nucleotide diversity between islands. The elevated heterozygosity on Tobago is maintained by predominantly clonal reproduction of hybrids formed from two diverged genomes. Hybridization has been followed by spread of the hybrids across the island, implying a selective advantage compared to native genotypes. Our results thus highlight that a single outcrossing event may be independently sufficient to cause pathogen expansion.
Reconstitution of intestinal stem cell nichein vitrowith pharmacological inhibitors or L-WRN conditioned medium differentially regulates epithelial proliferation, differentiation and barrier function in rabbit caecum organoids
Authors: Mussard Eloïse , Pouzet Cécile , Helies Virginie , Pascal Géraldine , Fourre Sandra , Cherbuy Claire , Rubio Aude , Vergnolle Nathalie , Combes Sylvie , Beaumont Martin 
Published: April 2020

AbstractIntestinal organoids are self-organized 3-dimensional (3D) structures formed by a single layer of polarized epithelial cells. This innovativein vitromodel is highly relevant to study physiology of the intestinal epithelium and its role in nutrition and barrier function. However, this model has never been developed in rabbits, while it would have potential applications for biomedical and veterinary research. Here, we cultured rabbit caecum organoids with either pharmacological inhibitors (2Ki medium) or L-WRN cells conditioned medium (L-WRN CM) to reconstitute the intestinal stem cell nichein vitro. Large spherical organoids were obtained with the 2Ki medium and this morphology was associated with a high level of proliferation and stem cells markers gene expression. In contrast, organoids cultured with L-WRN CM had a smaller diameter; a greater cell height and part of them were not spherical. When the L-WRN CM was used at low concentration (5%) for two days, the gene expression of stem cells and proliferation markers were very low, while absorptive and secretory cells markers and antimicrobial peptides were elevated. Epithelial cells within organoids were polarized in 3D cultures with 2Ki medium or L-WRN CM (apical side towards the lumen). We cultured dissociated organoid cells in 2D monolayers, which allowed accessibility to the apical compartment. Under these conditions, actin stress fibers were observed with the 2Ki medium, while perijonctionnal localization of actin was observed with the L-WRN CM suggesting, in 2D cultures as well, a higher differentiation level in the presence of L-WRN CM. In conclusion, rabbit caecum organoids cultured with the 2Ki medium were more proliferative and less differentiated than organoids cultured with L-WRN CM. We propose that organoids cultured with the 2Ki medium could be used to rapidly generatein vitroa large number of rabbit intestinal epithelial stem cells while organoids cultured with the L-WRN CM represent a suitable model to study differentiated rabbit epithelium.
Identifying different types of tumors in human brain, breast, and uterus according to their optical properties in the red to near-infrared region
Authors: Hamdy Omnia 
Published: April 2020

AbstractOptical diagnosis techniques are gaining validity due to their competitive advantages including safety and functionality. These methods probe the tissue using light in the red to near-infrared region that shows relatively high penetration in biological tissues. The reflected light which is controlled by tissue absorption and scattering parameters can provide significant information about its pathology. In the present work, a method for identifying different types of tumors in human brain, breast and uterus based on their absorption and scattering characteristics in the red to near-infrared spectra is proposed. The classification method depends on studying the red to near-infrared light diffusion through the examined tissues using Monte-Carlo simulation and finite element solution of the light diffusion equation. The obtained tissue reflectance profiles, optical fluence rate distribution and absorbed faction in each tumor type show different characteristics along the selected wavelengths. The variation in these three features can be considered as an alternative approach of medical diagnosis or can assist with other conventional diagnosis methods.
Prospects for detecting early warning signals in discrete event sequence data: application to epidemiological incidence data
Authors: Southall Emma , Tildesley Michael J. , Dyson Louise 
Published: April 2020

AbstractEarly warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators.Author summaryThe threat posed by infectious diseases has a huge impact on our global society. It is therefore critical to monitor infectious diseases as new data become available during control campaigns. One obstacle in observing disease emergence or elimination is understanding what influences noise in the data and how this fluctuates when near to zero cases. The standard data type collected is the number of new cases per day/month/year but mathematical modellers often focus on data such as the total number of infectious people, due to its analytical properties. We have developed a methodology to monitor the standard type of data to inform whether a disease is approaching emergence or disease elimination. We have shown computationally how fluctuations change as disease data get closer towards a tipping point and our insights highlight how these observed changes can be strikingly different when calculated on different types of data.
Tadpoles of hybridising fire-bellied toads (B. bombinaandB. variegata) differ in their susceptibility to predation
Authors: Smolinský Radovan , Baláž Vojtech , Nürnberger Beate 
Published: April 2020

AbstractThe role of adaptive divergence in the formation of new species has been the subject of much recent debate. The most direct evidence comes from traits that can be shown to have diverged under natural selection and that now contribute to reproductive isolation. Here, we make the case for differential adaptation of two fire-bellied toads (Anura, Bombinatoridae) to two types of aquatic habitat.Bombina bombinaandB. variegataare two anciently diverged taxa that now reproduce in predator-rich ponds and ephemeral aquatic sites, respectively. Nevertheless, they hybridise extensively wherever their distribution ranges adjoin. We show in laboratory experiments that, as expected,B. variegatatadpoles are at relatively greater risk of predation from dragonfly larvae, even when they display a predator-induced phenotype. These tadpoles spent relatively more time swimming and so prompted more attacks from the visually hunting predators. We predict that genomic regions linked to high activity inB. variegataare barred from introgression into theB. bombinagene pool and thus contribute to gene flow barriers that keep the two taxa from merging into one.