bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple random phosphorylations in clock proteins provide long delays and switches
Authors: Upadhyay Abhishek , Marzoll Daniela , Diernfellner Axel , Brunner Michael , Herzel Hanspeter 
Published: June 2020

AbstractTheory predicts that self-sustained oscillations require robust delays and nonlinearities (ultrasensitivity). Delayed negative feedback loops with switch-like inhibition of transcription constitute the core of eukaryotic circadian clock. The kinetics of core clock proteins such as PER2 in mammals and FRQ inNeurospora crassais governed by multiple phosphorylations. We investigate how multiple, slow and random phosphorylations control delay and molecular switches. We model phosphorylations of intrinsically disordered clock proteins (IDPs) using conceptual models of sequential and distributive phosphorylations. Our models help to understand the underlying mechanisms leading to delays and ultrasensitivity. The model shows temporal and steady state switches for the free kinase and the phosphoprotein. We show that random phosphorylations and sequestration mechanisms allow high Hill coefficients required for self-sustained oscillations.
Overcoming sparseness of biomedical networks to identify drug repositioning candidates
Authors: Poleksic Aleksandar 
Published: June 2020

AbstractModeling complex biological systems is necessary to understand biochemical interactions behind pharmacological effects of drugs. Successfulin silicodrug repurposing requires a thorough exploration of diverse biochemical concepts and their relationships, including drug’s adverse reactions, drug targets, disease symptoms, as well as disease associated genes and their pathways, to name a few. We present a computational method for inferring drug-disease associations from complex but incomplete and biased biological networks. Our method employs the compressed sensing technique to overcome the sparseness of biomedical data and, in turn, to enrich the set of verified relationships between different biomedical entities. We present a strategy for identifying network paths supportive of drug efficacy as well as a computational procedure capable of combining different network patterns to better distinguish treatments from non-treatments. The data and programs are freely available athttp://bioinfo.cs.uni.edu/AEONET.html.
Establishing the construct validity and Internal consistency for Urdu version of Jefferson Scale of Empathy-S (JSE-S)
Authors: Muhammad Syed Razi 
Published: June 2020

AbstractBACKGROUND AND OBJECTIVESEmpathy is an important factor in patient–physician relationship that results in better patient compliance, satisfaction, and clinical outcomes. Jefferson Scale of Empathy (JSE) assesses empathy in health professionals (HP-version) and related students (S-version). It has been translated in over 50 languages and validation studies have been performed on these translated S-version of the scale. We decided to examine empathy of Pakistani student and to study factor structure and psychometric properties of the Urdu translation of the JSE-S.METHODS405 out of 521 students of Muhammad Medical College participated in the study. It was a cross-sectional study and the students filled in Urdu version of JSE-S questionnaire consisting of 20 items. Each item was scored on 7-points Likert scale. Total scores ranged from 20 to 140. Higher values indicated more positive attitudes toward empathic patient care, and therefore a higher degree of empathyRESULTSThe mean JSE-S empathy score of the medical students was 107.22 (+/- 12.844). Cronbach’s alpha coefficient was 0.684 for the overall measure. Kaiser-Meyer-Olkin (KMO) test yielded an index of 0.764, suggesting a support for factor analysis. Bartlett’s test of sphericity was 985.518 and was highly significant (P = 000). A principal component analysis showed a three-factor solution that also provided support for the construct validity of the Urdu version of JSE S-version.CONCLUSIONThe Urdu version of JSE is a valid and reliable measure to tap empathy in a Pakistani medical student.
Presenting features of COVID-19 in older people: relationships with frailty, inflammation and mortality
Authors: Knopp Paul , Miles Amy , Webb Thomas E , Mcloughlin Benjamin C , Mannan Imran , Raja Nadia , Wan Bettina , Davis Daniel 
Published: June 2020

AbstractPurposeTo describe the clinical features of COVID-19 in older adults, and relate these to outcomes.MethodsCohort study of 217 individuals (≥70 years) hospitalised with COVID-19, followed up for allcause mortality. Secondary outcomes included cognitive and physical function at discharge. C-reactive protein and neutrophil: lymphocyte ratio were used as measures of immune activity.ResultsCardinal COVID-19 symptoms (fever, dyspnoea, cough) were common but not universal. Inflammation on hospitalisation was lower in frail older adults. Fever, dyspnoea, delirium and inflammation were associated with mortality. Delirium at presentation was an independent risk factor for cognitive decline at discharge.ConclusionsCOVID-19 may present without cardinal symptoms as well as implicate a possible role for age-related changes in immunity in mediating the relationship between frailty and mortality.Key summary pointsAimTo characterise symptoms, key findings and clinical outcomes in older adults with COVID-19Findings12% of older individuals did not present with classical COVID-19 symptoms, though fever, dyspnoea, delirium and raised inflammation were associated with higher mortality. Compared with fitter older individuals, immune activity was lower in frailer patients.MessageCOVID-19 may present without cardinal symptoms as well as implicate a possible role for age-related changes in immunity in mediating the relationship between frailty and mortality.
Analysis of the effect of proton pump inhibitors on the course of common COVID-19
Authors: Zhang Xiao-Yu , Wu Hai-Bing , Ling Yun , Qian Zhi-Ping , Chen Liang 
Published: June 2020

ABSTRACTBackground/aimsTo evaluate the effect of proton pump inhibitors on the course of common COVID-19.MethodsClinical data of common COVID-19 patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses.ResultsA total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05.ConclusionProton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19.
Survival and predictors of deaths of patients hospitalized due to COVID-19 from a retrospective and multicenter cohort study in Brazil
Authors: Santos Marquiony M , Lucena Eudes ES , Lima Kenio C , Brito Andiara AC , Bay Monica B , Bonfada Diego 
Published: June 2020

AbstractThe epidemic caused by COVID-19 in Brazil is associated with an unfavorable political scenario, aggravated by intense social inequality and low number of available hospital beds. Therefore, this study aimed to analyze the survival of patients admitted to Brazilian hospitals due to the COVID-19 and estimate prognostic factors. This is a retrospective, multicenter cohort study, based on data from 46285 hospitalizations for COVID-19 in Brazil. Survival functions were calculated using the Kaplan-Meier’s method. The Log-rank test compared the survival functions for each variable and from that, hazard ratios were calculated and the proportional hazards model was used in Cox multiple regression. The smallest survival curves were the ones for patients at the age of 68 years or more, black / brown race, illiterate, living in the countryside, dyspnea, respiratory distress, influenza-like outbreak, O2 saturation <95%, X-ray change, length of stay in the ICU, invasive ventilatory support, previous heart disease, pneumopathy, diabetes, down’s syndrome, neurological disease and kidney disease. Better survival was observed in the symptoms and in an asthmatic patient. The multiple model for increased risk of death when they were admitted to the ICU HR 1.28 (95% CI 1.21–1.35), diabetes HR 1.17 (95% CI 1.11–1.24), neurological disease HR 1.34 (95% CI 1.22–1.46), kidney disease HR 1.11 (95% CI 1.02–1.21), heart disease HR 1.14 (95% CI 1.08–1.20), black or brown race of HR 1.50 (95% CI 1.43–1.58), asthma HR 0.71 (95% CI 0.61–0.81) and pneumopathy HR 1.12 (95% CI 1.02–1.23). The overall survival time was low in hospitalizations for COVID-19 and this reinforces the importance of sociodemographic and clinical factors as a prognosis for death. The lack of a protocol for scientific clinical management puts a greater risk of death for about 80 million Brazilians, who are chronically ill or living in poverty. COVID-19 can promote selective mortality that borders the eugenics of specific social segments in Brazil.
Amount of fiction reading correlates with higher connectivity between cortical areas for language and mentalizing
Authors: Hartung Franziska , Willems Roel M. 
Published: June 2020

AbstractBehavioral evidence suggests that engaging with fiction is positively correlated with social abilities. The rationale behind this link is that engaging with fiction and fictional characters may offer a ‘training mode’ for mentalizing and empathizing with sentient agents in the real world, analogous to a flight simulator for pilots. In this study, we explored the relationship between reading fiction and mentalizing by looking at brain network dynamics in 57 participants who varied on how much fiction they read in their daily lives. The hypothesis was that if reading fiction indeed trains mentalizing, a task that requires mentalizing –Like immersing in a fictional story and engaging with a protagonist-should elicit differences in brain network dynamics depending on how much people read. More specifically, more frequent readers should show increased connectivity within the theory of mind network (ToM) or between the ToM network and other brain networks. While brain activation was measured with fMRI, participants listened to two literary narratives. We computed time-course correlations between brain regions and compared the correlation values from listening to narratives to listening to an auditory baseline condition. The between-region correlations were then related to individual differences measures including the amount of fiction that participants consume in their daily lives. Our results show that there is a linear relationship between how much people read and the functional connectivity in areas known to be involved in language and mentalizing. This adds neurobiological credibility to the ‘fiction influences mentalizing abilities’ hypothesis as suggested on the basis of conceptual analysis.
BioDynaMo: a general platform for scalable agent-based simulation
Authors: Breitwieser Lukas , Hesam Ahmad , de Montigny Jean , Vavourakis Vasileios , Iosif Alexandros , Jennings Jack , Kaiser Marcus , Manca Marco , Di Meglio Alberto , Al-Ars Zaid , Rademakers Fons , Mutlu Onur , Bauer Roman 
Published: June 2020

AbstractMotivationAgent-based modeling is an indispensable tool for studying complex biological systems. However, existing simulators do not always take full advantage of modern hardware and often have a field-specific software design.ResultsWe present a novel simulation platform called BioDynaMo that alleviates both of these problems. BioDynaMo features a general-purpose and high-performance simulation engine. We demonstrate that BioDynaMo can be used to simulate use cases in: neuroscience, oncology, and epidemiology. For each use case we validate our findings with experimental data or an analytical solution. Our performance results show that BioDynaMo performs up to three orders of magnitude faster than the state-of-the-art baseline. This improvement makes it feasible to simulate each use case with one billion agents on a single server, showcasing the potential BioDynaMo has for computational biology research.AvailabilityBioDynaMo is an open-source project under the Apache 2.0 license and is available atwww.biodynamo.org. Instructions to reproduce the results are available in supplementary information.Contactlukas.breitwieser@inf.ethz.ch,a.s.hesam@tudelft.nl,omutlu@ethz.ch,r.bauer@surrey.ac.ukSupplementary informationAvailable athttps://doi.org/10.5281/zenodo.4501515.
In-Ear SpO2: A Tool for Wearable, Unobtrusive Monitoring of Hypoxaemia in COVID-19
Authors: Davies Harry J. , Williams Ian , Peters Nicholas S. , Mandic Danilo P. 
Published: June 2020

AbstractNon-invasive ambulatory estimation of blood oxygen saturation has emerged as an important clinical requirement to detect hypoxemia in the delayed post-infective phase of COVID-19, where dangerous hypoxia may occur in the absence of subjective breathlessness. This immediate clinical driver, combined with the general quest for more personalised health data, means that pulse oximetry measurement of capillary oxygen saturation (SpO2) will likely expand into both the clinical and consumer market of wearable health technology in the near future. In this study, we set out to establish the feasibility of SpO2measurement from the ear canal as a convenient site for long term monitoring, and perform a comprehensive comparison with the right index finger - the conventional clinical measurement site. During resting blood oxygen saturation estimation, we found a root mean square difference of 1.47% between the two measurement sites, with a mean difference of 0.23% higher SpO2in the right ear canal. Through the simultaneous recording of pulse oximetry from both the right ear canal and index finger during breath holds, we observe a substantial improvement in response time between the ear and finger that has a mean of 12.4 seconds and a range of 4.2 - 24.2 seconds across all subjects. Factors which influence this response time, termed SpO2delay, such as the sex of a subject are also explored. Furthermore, we examine the potential downsides of ear canal blood oxygen saturation measurement, namely the lower photoplethysmogram amplitude, and suggest ways to mitigate this disadvantage. These results are presented in conjunction with previously discovered benefits such as robustness to temperature, making the case for measurement of SpO2from the ear canal being both convenient and superior to conventional finger measurement sites for continuous nonintrusive long term monitoring in both clinical and everyday-life settings.
Exploring the correlation between COVID-19 fatalities and poor WASH (Water, Sanitation and Hygiene) services
Authors: Amankwaa Godfred , Fischer Christian 
Published: June 2020

AbstractAccess to safe Water, Sanitation and Hygiene (WASH) services have been recognized as a highly precautionary measure essential to protecting human health during this COVID-19 outbreak. However, it is currently unknown whether poor or non-availability of these services are also closely related to COVID-19 fatalities. We analysed the latest data on COVID-19 fatality rates in Sub Saharan Africa with indicators of safe water and sanitation governance to test this hypothesis. We found a strong correlation between a higher case fatality rate and poorer access to safe drinking water as well as safe sanitation. The Pearson correlation is stronger for access to safe sanitation (−0.30) compared to access to safe drinking water (−0.20). The Chad, Niger and Sierra Leone were amongst the countries with the highest fatality rates (>6.0) and also had particularly poor access to safe drinking water (<34%) and safe sanitation (<22%). The hypothesis of an association between COVID-19 fatalities and poor access to water and sanitation was confirmed by this study. However, our analysis does not establish causality. Given the increase spread of COVID-19 and related deaths, this analysis serves as an important reminder that safe water and sanitation services are key for public health interventions and highlights the need to prioritise this sector in all economies.
Intimate Partner Violence Victimization and Perpetration among U.S. Adults during COVID-19: A Brief Report
Authors: Davis Maxine , Gilbar Ohad , Padilla-Medina Diana 
Published: June 2020

ABSTRACTImportanceAnecdotal evidence such as increased calls to domestic violence (DV) hotlines across the globe suggest that there may be an increase of IPV prevalence in association with the COVID-19 outbreak; however, no study has investigated this phenomenon empirically.ObjectiveTo evaluate the association between COVID-19 related conditions and recent use or experience of IPV (since the pandemic outbreak in the U.S).Design, Setting, and ParticipantsThis cross-sectional study analyzed data collected online from a sample of noninstitutionalized adults (age 18+) in the U.S. (N=2,045). More than half of the sample self-identified as being in an intimate relationship at the time of the study.Main Outcomes and MeasuresA four-item tool was used to assess IPV perpetration and victimization since the outbreak of COVID-19. The rapid tool inquired about two forms of IPV, psychological and physical. Participants self-reported demographic data and recent health histories, including COVID-19 tests results, related symptoms and degree of personal social distancing. We hypothesized that COVID-19 related factors would increase risks of IPV.ResultsIn this study, self-reported COVID-19 impacted respondents had an increased risk of IPV victimization and perpetration. Among those who reported having symptoms consistent with coronavirus, but were denied access to testing, psychological IPV victimization was 3 times greater than those who did not (Exp[B] =3.15, [1.19, 2.29] p <.05). For participants who reported testing positive to COVID-19, the odds of using psychological IPV (Exp[B] =3.24, [1.18, 8.89] p <.05) and physical IPV (Exp[B]=3.02, [1.12, 8.17] p <.05) against an intimate partner increased by more than 3 times.Conclusions and RelevancePatient education and community outreach/health care system initiatives focused on IPV risk behaviors may help reduce the potential development of IPV. Continued surveillance is imperative to improve health and well-being along with effective intervention development and implementation.
More than privacy: Australians’ concerns and misconceptions about the COVIDSafe App
Authors: Thomas Rae , Michaleff Zoe A , Greenwood Hannah , Abukmail Eman , Glasziou Paul 
Published: June 2020

AbstractBackgroundTimely and effective contact tracing is an essential public health role to curb the transmission of COVID-19. App-based contact tracing has the potential to optimise the resources of overstretched public health departments. However, it’s efficiency is dependent on wide-spread adoption. We aimed to identify the proportion of people who had downloaded the Australian Government COVIDSafe app and examine the reasons why some did not.MethodAn online national survey with representative quotas for age and gender was conducted between May 8 and May 11 2020. Participants were excluded if they were a healthcare professional or had been tested for COVID-19.ResultsOf the 1802 potential participants contacted, 289 were excluded, 13 declined, and 1500 participated in the survey (response rate 83%). Of survey participants, 37% had downloaded the COVIDSafe app, 19% intended to, 28% refused, and 16% were undecided. Equally proportioned reasons for not downloading the app included privacy (25%) and technical concerns (24%). Other reasons included a belief that social distancing was sufficient and the app is unnecessary (16%), distrust in the Government (11%), and apathy (11%). In addition, COVIDSafe knowledge varied with confusion about its purpose and capabilities.ConclusionFor the COVIDSafe app to be accepted by the public and used correctly, public health messages need to address the concerns of its citizens, specifically in regards to privacy, data storage, and technical capabilities. Understanding the specific barriers preventing the uptake of tracing apps provides the opportunity to design targeted communication strategies aimed at strengthening public health initiatives such as download and correct use.
X-ray phase contrast tomography for the investigation of amyotrophic lateral sclerosis
Authors: Begani Provinciali Ginevra , Pieroni Nicola , Bukreeva Inna , Fratini Michela , Massimi Lorenzo , Maugeri Laura , Palermo Francesca , Bardelli Fabrizio , Mittone Alberto , Bravin Alberto , Gigli Giuseppe , Gentile Francesco , Fossaghi Andrea , Riva Nilo , Quattrini Angelo , Cedola Alessia 
Published: June 2020

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.