bluuebunny/crossref_metadata_2025 huggingface dataset:
CD47 prevents the elimination of diseased fibroblasts in scleroderma
Authors: Lerbs Tristan , Cui Lu , King Megan E. , Chai Tim , Muscat Claire , Shibata Tyler , Wernig Gerlinde
Published: June 2020

Scleroderma is a devastating fibrotic autoimmune disease. Current treatments are partly effective in preventing disease progression, but do not remove fibrotic tissue. Here, we evaluated whether scleroderma fibroblasts take advantage of the “don’t-eat-me-signal” CD47 and whether blocking CD47 enables the body’s immune system to get rid of diseased fibroblasts. To test this approach, we used aJun-inducible scleroderma model. We first demonstrated in patient samples that scleroderma upregulated JUN and increased promotor accessibilities of both JUN and the CD47. Next, we established our scleroderma model demonstrating thatJunmediated skin fibrosis through the hedgehog-dependent expansion of CD26+Sca1-fibroblasts in mice. In a niche-independent adaptive transfer model, JUN steered graft survival and conferred increased self-renewal to fibroblasts. In vivo, JUN enhanced the expression of CD47, and inhibiting CD47 eliminated an ectopic fibroblast graft and increased in vitro phagocytosis. In the syngeneic mouse, depleting macrophages ameliorated skin fibrosis. Therapeutically, combined CD47 and IL6 blockade reversed skin fibrosis in mice and led to the rapid elimination of ectopically transplanted scleroderma cells. Altogether, our study is the first to demonstrate the efficiency of combining different immunotherapies in treating scleroderma and provide a rationale for combining CD47 and IL6 inhibition in clinical trials.
Characterization of alkaline stress tolerance mechanisms inLotusforage species modulated byPantoea eucalypti
Authors: Campestre Maria Paula , Castagno Nazareno Luis , Antonelli Cristian Javier , Maguire Vanina Giselle , Escaray Francisco Jose , Ruiz Oscar Adolfo
Published: June 2020

This study was designed to elucidate the physiological responses of threeLotusforage accessions to alkaline stress and the influence of the inoculation of aPantoea eucalyptiendophyte strain on its mitigation. One-month-old diploid accessions ofLotus corniculatus(Lc) andLotus tenuis(Lt), and the interspecific hybrid LtxLc obtained from these parental accessions, were exposed to alkaline stress (pH 8.2) by the addition of NaHCO310 mM to the nutrient solution for 2 weeks. The results indicated that Lt and the LtxLc hybrid are alkaline-tolerant compared to Lc, based on the observation that their dry mass is not reduced under stress, and symptoms of chlorosis do not appear on leaf blades, in contrast to observations of the Lc accession subjected to identical growth and stress conditions. In Lc and LtxLc accessions, the Fe2+concentration decreased in the aerial part under stress and increased in the roots. Interveinal chlorosis observed in the youngest leaves of Lc during alkaline treatment was accompanied with a higher reduction of Fe2+levels in shoots and a higher increment of Fe2+in roots, compared to the other accession. Plant inoculation also tended to acidify the medium under alkalinity, contributing to Fe accumulation in the roots. Moreover, the inoculation caused a considerable increase in Fe2+content in shoots in all threeLotusforage species under alkaline treatment.

Fv/Fmand PIABSwere only reduced in Lc under alkaline treatment. Inoculation reverted this effect and improved the ABS/RC and DIo/RC ratios in all three accessions. In addition, under alkaline conditions, Lc dissipated more energy than control plants. Expression of the metal-transporting gene NRAMP1 increased in the inoculated Lc accession under stress, while remaining unmodified in Lt and LtxLc hybrid.

Altogether, the results obtained make clear the importance of inoculation withP. eucalypti, which contributed significantly to the mitigation of alkaline stress. Thus, all the results provide useful information for improving alkaline tolerance traits inLotusforage species and their interspecific hybrids.
When to be a male? Role of resource-limitation and pollinators in determining floral sex in an andromonoecious spiderwort
Authors: Albal Asawari , Azad G , Shrotri Saket , Gowda Vinita
Published: June 2020

The evolution and maintenance of sexual systems in plants is often driven by resource allocation and pollinator preferences, and very little is known about their role in determining floral sex expression in plants. In annual, entomophilous plants three major constraints can be identified towards optimal reproduction: 1) nutrient resources available from the environment, 2) nutrient resources allocated towards reproduction, i.e., fruits vs. flowers, and 3) pollinator visitations.

Andromonoecy is a sexual system where plants bear both staminate and hermaphrodite flowers on the same inflorescence. The optimal resource allocation hypothesis suggests that under nutrient constraints, plants will produce more male flowers since they are energetically cheaper to produce over the more expensive hermaphrodite flowers. We test this hypothesis in the andromonoeciousMurdannia simplex(Commelinaceae) by quantifying male and hermaphrodite flowers in a natural population and contrasting the distribution of the two sexes in plants from two resource conditions (stream population vs. plateau population). We next carried out choice experiments to test pollinator preference towards a specific sex.

We found that inM. simplex, production of hermaphrodite flowers is resource-dependent and under resource constraints fewer numbers of flowers were produced and most of them were males. We failed to observe pollinator preference towards either sex butAmegilla spp. andApis ceranashowed higher visitation towards the most abundant sex within a trial, suggesting frequency-dependent visitation. Thus, we conclude that environmentally driven resource constraints play a bigger role in driving floral sex expression inMurdanniaover direct pollinator-driven constraints.
Public health interventions in India slowed the spread of COVID-19 epidemic dynamics
Authors: Singh Balbir B , Lowerison Mark , Lewinson Ryan T. , Vallerand Isabelle A. , Deardon Rob , Gill Játinder PS , Gill Baljit Singh , Barkema Herman W
Published: June 2020

Background

The government of India implemented social distancing interventions to contain the COVID-19 epidemic. However, effects on epidemic dynamics are yet to be understood.

Methods

Rates of laboratory-confirmed COVID-19 infections per day and effective reproduction number (Rt) were estimated for 4 periods (Pre-lockdown and Lockdown Phases 1 to 3) according to nationally implemented phased interventions. Adoption of these interventions was estimated using Google mobility data. Estimates at the national level and for 12 Indian states most affected by COVID-19 are presented.

Findings

Daily case rates ranged from 0·03 to 30·05/10 million people across 4 discrete periods in India. From May 4-17, 2020, the National Capital Territory (NCT) of Delhi had the highest case rate (222/10 million people/day), whereas Kerala had the lowest (2·18/10 million/day). AverageRtwas 1·99 (95% CI 1·93-2·06) for India; it ranged from 1·38 to 2·78, decreasing over time. Median mobility in India decreased in all contact domains, with the lowest being 21% in retail/recreation (95% CI 13-46%), except home which increased to 129% (95% CI 117-132%) compared to the 100% baseline value.

Interpretation

The Indian government imposed strict contact mitigation, followed by a phased relaxation, which slowed the spread of COVID-19 epidemic progression in India. The identified daily COVID-19 case rates andRtwill aid national and state governments in formulating ongoing COVID-19 containment plans. Furthermore, these findings may inform COVID-19 public health policy in developing countries with similar settings to India.

Funding

Non-funded.
CLINICAL PROPERTIES AND DIAGNOSTIC METHODS OF COVID-19 INFECTION IN PREGNANCIES: META-ANALYSIS
Authors: Uygun-Can Banu , Acar-Bolat Bilge
Published: June 2020

We aimed to summarize reliable medical evidence by the meta-analysis of all published retrospective studies that examined data based on the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by clinical symptoms, molecular (RT-PCR) diagnosis and characteristic CT imaging features in pregnant women. MEDLINE PubMed, SCOPUS, ISI Web of Science, Clinical Key, and CINAHL databases were used to select the studies. Then, 384 articles were received, including the studies until 01/MAY/2020. As a result of the full-text evaluation, 12 retrospective articles covering all the data related were selected. A total of 181 pregnant cases with SARS-CoV-2 infections were included in the meta-analysis within the scope of these articles. According to the results, the incidence of fever was 38.1% (95% CI: 14.2–65%), and cough was 22% (95% CI: 10.8–35.2%) among all clinical features of pregnant cases with SARS-CoV-2 infection. So, fever and cough are the most common symptoms in pregnant cases with SARS-CoV- infection, and 91.8% (95% CI: 76.7–99.9%) of RT-PCR results are positive. Moreover, abnormal CT incidence is 97.9% (95% CI: 94.2–99.9%) positive. No case was death. However, as this virus spreads globally, it should not be overlooked that the incidence will increase in pregnant women and may be in the risky group. RT-PCR and CT can be used together in an accurate and safe diagnosis. In conclusion, these findings will provide important guidance for current studies regarding the clinical features and correct detection of SARS-CoV-2 infection in pregnant women, as well as whether it will create emergency tables that will require the use of a viral drug.
The effect of strict lock down measures on Covid-19 seroprevalence rate and herd immunity
Authors: Sughayer Maher A. , Mansour Asem , Nuirat Abeer Al , Souan Lina , Ghanem Mohammad , Siag Mahmoud
Published: June 2020

Background

Covid-19 seroprevalence rates and serological tests are important tools in understanding the epidemiology of the disease and help in the fight against it. Seroprevalence rates vary according to the population studied and the test employed and they range from 0.133 to 25.7%. The purpose of this study is to assess the seroprevalence rate in a population of healthy blood donors living under strict lockdown measures in Jordan which has in total 144 confirmed cases per million population.

Methods

Left-over sera and plasma samples from 746 healthy blood donors were tested using a commercially available FDA approved kit having a sensitivity and specificity of 100% and 99.8% respectively. External positive controls were used for validation.

Results

More than 80% of the donors were men 18-63 year old and residing in the capital city of Jordan, Amman. All tested specimens were negative yielding a zero seroprevalence rate in this healthy blood donor population.

Conclusion

Strict lockdown measures effectively limit intracommunity spread of the infection, however at the cost of lack of any acquired community immunity. Additionally the use of highly specific test is recommended in low prevalence setting.
Effect of metabolic syndrome components on the risk of malignancy in patients with gallbladder lesions
Authors: Deng Zheng , Xuan Yan , Li Xinxing , Crawford William J , Yuan Zhiqing , Chen Zhoukan , Brooks Anastasia , Liang Xiaowen , Wang Haolu , Chen Tao
Published: June 2020

Background and Aims

The malignant potential of gallbladder lesions is debated, and there is limited guidance on surveillance. Predicting their risk of malignancy could help clinicians manage and potentially improve prognosis. We evaluated the independent and joint effects of metabolic syndrome components on the risk of malignancy among patients with gallbladder lesions.

Methods

Using a multicenter database, consecutive patients with pathologically confirmed gallbladder lesions between 2012 and 2019 were identified. Univariate and multivariate logistic regression analyses were used to evaluate the effects of metabolic syndrome components (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators for the risk of malignancy. Unadjusted and adjusted odds ratios were calculated.

Results

Of the 625 patients, 567 patients were identified with benign gallbladder lesions and 58 patients with gallbladder cancer (GBC). Among all metabolic syndrome components, the proportion of GBC patients with dyslipidemia (63.8%) was significantly greater than benign gallbladder polyps (42.2%, P = 0.002). In multivariate logistic regression analysis, dyslipidemia was associated with a 2.67-fold increase in the risk of GBC (95% confidence interval 1.17-6.09). Dyslipidemia is an independent risk factor for malignancy (adjusted odds ratio 2.164, 95% confidence interval 1.165-4.021), regardless of whether the other risk factors and metabolic syndrome components are combined. Dyslipidemia (adjusted odds ratio 2.164, 95% confidence interval 1.165-4.021) and decreased high-density lipoprotein (HDL, adjusted odds ratio 3.035, 95% confidence interval 1.645-5.600) were closely associated with increased risk of malignancy.

Conclusions

Dyslipidemia is associated with a 2.67-fold increase in the risk of malignancy, regardless of the presence of other metabolic syndrome components. Dyslipidemia is an independent risk factor for malignancy in patients with gallbladder lesions.
Kidney Biomarkers and Major Adverse Kidney Events in Critically Ill Patients
Authors: Flannery Alexander H. , Bosler Katherine , Ortiz-Soriano Victor , Gianella Fabiola , Prado Victor , Toto Robert D. , Moe Orson W. , Neyra Javier A.
Published: June 2020

Background

Several biomarkers of acute kidney injury (AKI) have been examined for their ability to predict AKI earlier than serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research.

Methods

Single-center prospective study collecting blood and urine samples from critically ill patients with AKI KDIGO stage 2 or above, and matched controls from a single, tertiary care intensive care unit. Samples were collected at 24-48 hours after AKI diagnosis (cases) or ICU admission (controls), 5-7 days later, and 4-6 weeks following discharge for AKI patients. The primary outcome of interest was MAKE at hospital discharge.

Results

Serum/urinary neutrophil gelatinase-associated lipocalin, serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE compared to those not experiencing MAKE at hospital discharge. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a clinical prediction model of MAKE as assessed by the area under the receiver operating characteristic curve.

Patients without MAKE experienced a greater decline in serum NGAL from initial measurement to second measurement than those patients experiencing MAKE.

Conclusion

Early measures of kidney biomarkers in critically ill patients are associated with MAKE. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE.
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

Theory 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

Modeling 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

BACKGROUND AND OBJECTIVES

Empathy 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.

METHODS

405 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 empathy

RESULTS

The 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.

CONCLUSION

The 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

Purpose

To describe the clinical features of COVID-19 in older adults, and relate these to outcomes.

Methods

Cohort 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.

Results

Cardinal 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.

Conclusions

COVID-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 points

Aim

To characterise symptoms, key findings and clinical outcomes in older adults with COVID-19

Findings

12% 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.

Message

COVID-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

Background/aims

To evaluate the effect of proton pump inhibitors on the course of common COVID-19.

Methods

Clinical 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.

Results

A 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.

Conclusion

Proton 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

The 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

Behavioral 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

Motivation

Agent-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.

Results

We 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.

Availability

BioDynaMo 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.

Contact

lukas.breitwieser@inf.ethz.ch,a.s.hesam@tudelft.nl,omutlu@ethz.ch,r.bauer@surrey.ac.uk

Supplementary information

Available athttps://doi.org/10.5281/zenodo.4501515.
No Evidence for Reduced Hospital Admissions or Increased Deaths from Stroke or Heart Attack During COVID-19
Authors: Reeves Katharine , Watson Samuel , Pankhurst Tanya , Khunti Kamlesh , Gallier Suzy , Skrybant Magdalena , Chilton Peter J , Lilford Richard J
Published: June 2020

Articles in the UK press have claimed that hospital admissions for heart attack and stroke have declined during the COVID-19 pandemic. However, data from the West Midlands Ambulance Service have not shown any reduction in call-outs for patients with stroke or ST-Elevation Myocardial Infarction. This study examined data from University Hospital Birmingham NHS Foundation Trust, comparing admissions from week 1 of 2016 to week 17 of 2019, with the same period in 2020, pre- and post-lockdown. The results showed that there was no evidence of a reduction in the overall mean number of admissions of patients with these conditions in the post-lockdown period.
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

Non-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.
Return of Results in Psychiatric Genetics Research: Perceptions of Best Practices in a Global Sample of Psychiatric Genetics Researchers
Authors: Lazaro-Munoz Gabriel , Torgerson Laura N. , Pereira Stacey
Published: June 2020

Many research sponsors and genetic researchers agree that some medically relevant genetic findings should be offered to participants. The scarcity of research specific to returning genetic results related to psychiatric disorders hinders the ability to develop ethically-justified and empirically-informed guidelines for responsible return of results for these conditions. We surveyed 407 psychiatric genetics researchers from 39 countries to examine their perceptions of challenges to returning individual results and views about best practices for the process of offering and returning results. Most researchers believed that disclosure of results should be delayed if a patient-participant is experiencing significant psychiatric symptoms. Respondents felt that there is little research on the impact of returning results to participants with psychiatric disorders and agreed that return of psychiatric genetics results to patient-participants may lead to discrimination by insurance companies or other third parties. Almost half of researchers believed results should be returned through a participant's treating psychiatrist, but many felt that clinicians lack knowledge about how to manage genetic research results. Most researchers thought results should be disclosed by genetic counselors or medical geneticists and in person, however, almost half also supported disclosure via telemedicine. This is the first global survey to examine the perspectives of researchers with experience working with this patient population and with these conditions. Their perspectives can help inform the development of much-needed guidelines to promote responsible return of results related to psychiatric conditions to patients with psychiatric disorders.
Exploring the correlation between COVID-19 fatalities and poor WASH (Water, Sanitation and Hygiene) services
Authors: Amankwaa Godfred , Fischer Christian
Published: June 2020

Access 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

Importance

Anecdotal 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.

Objective

To 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 Participants

This 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 Measures

A 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.

Results

In 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 Relevance

Patient 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

Background

Timely 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.

Method

An 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.

Results

Of 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.

Conclusion

For 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.
Intellectual capital and knowledge generation: an empirical study from Colombian public universities
Authors: Salinas-Ávila John , Abreu-Ledón René , Tamayo-Arias Johnny
Published: June 2020

Purpose

The purpose of this paper is to provide empirical evidence on the relationships between the dimensions of intellectual capital (IC) and the generation of knowledge in public universities.

Design/methodology/approach

An online survey was developed and administered in Colombia. A total of 209 researchers participated in the study. Data were collected through IC measurements concerning the research mission of the universities. Scientific publications from the respondents and the citations received were taken as proxies for the generation of knowledge. To test the hypotheses, structural equation modeling was used.

Findings

Hypotheses proposing a positive association between the dimensions of IC, namely, human capital, structural capital, and relational capital, and the generation of knowledge were tested. The findings highlight that human capital is indirectly and positively related to the generation of knowledge through relational capital, as well as through the path of structural capital-relational capital.

Practical implications

The study suggests that directors of research at universities could improve the results of this activity by analyzing and understanding the dimensions of IC that contribute to the development of scientific capacities and the generation of knowledge.

Originality/value

This is one of the first studies that has examined the interrelationships between the dimensions of IC at universities and the generation of knowledge.
Are fish sensitive to trawling recovering in the Northeast Atlantic?
Authors: Rindorf Anna , Gislason Henrik , Burns Finlay , Ellis Jim R. , Reid David
Published: June 2020

The protection of sensitive species from overfishing is a key aspect of the ecosystem approach to fisheries management.

We use life‐history parameters and knowledge of fish shape and habitat to estimate the sensitivity of 270 species in the Northeast Atlantic to demersal trawling and compare sensitivity to the most recent IUCN categorization. Species classified as threatened were on average significantly more sensitive to trawling than other species. Using trawl surveys in European Atlantic waters from 36°N to 62°N, we estimated indicators of abundance of 31 highly sensitive species and compared changes in abundance to sensitivity, management measures, and value of landings.

The abundance of 23 of the 31 sensitive species increased after year 2000 with 14 of the species showing increases significant at the 5% level. The increases were not due to specific management measures, as less than half of the species were covered by catch limits. Furthermore, sensitivity or value of landings was not related to trends in abundance.

Three species (Atlantic wolf‐fish, tusk and starry ray) declined significantly. These species are all at their southern distributional limit in the North Sea.

Synthesis and applications. We recommend monitoring the development of sensitive species to identify species under pressure and allow rapid management actions before species enter the IUCN threatened category. Furthermore, we recommend taking precautions where species are under combined pressure from climate change and fishing.
Methyl‐compounds driven benthic carbon cycling in the sulfate‐reducing sediments of South China Sea
Authors: Xu Lei , Zhuang Guang‐Chao , Montgomery Andrew , Liang Qianyong , Joye Samantha B. , Wang Fengping
Published: June 2020

Methane is a potent greenhouse gas; methane production and consumption within seafloor sediments has generated intense interest. Anaerobic oxidation of methane (AOM) and methanogenesis (MOG) primarily occur at the depth of the sulfate–methane transition zone or underlying sediment respectively. Methanogenesis can also occur in the sulfate‐reducing sediments through the utilization of non‐competitive methylated compounds; however, the occurrence and importance of this process are not fully understood. Here, we combined a variety of data, including geochemical measurements, rate measurements and molecular analyses to demonstrate the presence of a cryptic methane cycle in sulfate‐reducing sediments from the continental shelf of the northern South China Sea. The abundance of methanogenic substrates as well as the high MOG rates from methylated compounds indicated that methylotrophic methanogenesis was the dominant methanogenic pathway; this conclusion was further supported by the presence of the methylotrophic genus Methanococcoides. High potential rates of AOM were observed in the sediments, indicating that methane produced in situ could be oxidized simultaneously by AOM, presumably by ANME‐2a/b as indicated by 16S rRNA gene analysis. A significant correlation between the relative abundance of methanogens and methanotrophs was observed over sediment depth, indicating that methylotrophic methanogenesis could potentially fuel AOM in this environment. In addition, higher potential rates of AOM than sulfate reduction rates at in situ methane conditions were observed, making alternative electron acceptors important to support AOM in sulfate‐reducing sediment. AOM rates were stimulated by the addition of Fe/Mn oxides, suggesting AOM could be partially coupled to metal oxide reduction. These results suggest that methyl‐compounds driven methane production drives a cryptic methane cycling and fuels AOM coupled to the reduction of sulfate and other electron acceptors.
The effects of national cultures on two technologically advanced countries: The case of e‐leadership in South Korea and the United States
Authors: Liu Cheol , Van Wart Montgomery , Kim Soonhee , Wang Xiaohu , McCarthy Alma , Ready David
Published: June 2020

The increased use of information and communication technologies (ICTs) has triggered enormous innovation in the public sector and created positive public value at the managerial, delivery of services, and policy levels. However, these positive outcomes do not automatically accrue simply by adoption of ICTs as public leaders can fail to adopt relevant new ICTs, use them poorly, or use them in ways that actually diminish public value, which raises the question of the importance of e‐leadership. This article examines e‐leadership and innovation capacity at the individual public manager level and fills in some gaps about the practice and implementation of ICTs in the public sector. We explore eight research questions useful in theorizing about e‐leadership, develop constructs of e‐leadership, and describe the current development of e‐leadership. By comparing e‐leadership in two country settings (South Korea and the United States), we also overcome the limitations of the existing Western‐oriented studies about innovations in the public sector. In addition to the growth of e‐leadership use and requirements for a variety of competencies equivalent to, but separate from, traditional communication competences, we find that national cultures exert significant influence on the major constructs of e‐leadership, which implies that an effective e‐leadership strategy should consider cultural contexts seriously.