bluuebunny/crossref_metadata_2025 huggingface dataset:
The contribution of evolutionary game theory to understanding and treating cancer
Authors: Wölfl Benjamin , te Rietmole Hedy , Salvioli Monica , Kaznatcheev Artem , Thuijsman Frank , Brown Joel S. , Burgering Boudewijn , Staňková Kateřina
Published: December 2020

Evolutionary game theory mathematically conceptualizes and analyzes biological interactions where one’s fitness not only depends on one’s own traits, but also on the traits of others. Typically, the individuals are not overtly rational and do not select, but rather inherit their traits. Cancer can be framed as such an evolutionary game, as it is composed of cells of heterogeneous types undergoing frequency-dependent selection. In this article, we first summarize existing works where evolutionary game theory has been employed in modeling cancer and improving its treatment. Some of these game-theoretic models suggest how one could anticipate and steer cancer’s eco-evolutionary dynamics into states more desirable for the patient via evolutionary therapies. Such therapies offer great promise for increasing patient survival and decreasing drug toxicity, as demonstrated by some recent studies and clinical trials. We discuss clinical relevance of the existing game-theoretic models of cancer and its treatment, and opportunities for future applications. Moreover, we discuss the developments in cancer biology that are needed to better utilize the full potential of game-theoretic models. Ultimately, we demonstrate that viewing tumors with an evolutionary game theory approach has medically useful implications that can inform and create a lockstep between empirical findings and mathematical modeling. We suggest that cancer progression is an evolutionary game and needs to be viewed as such.
ABO-RH blood group and risk of covid-19 in a moroccan population
Authors: Belaouni Mourad , Malki Elhoucine , Bahraouy Rabii El , Maliki Bouchra El , Er-Rami Mohammed , Louzi Houcine , Lahmadi Khalid
Published: December 2020

Introduction

Given the rapid spread, significant morbidity and mortality associated with COVID-19, there has been scientific interest in obtaining data detailing the factors influencing the risk of COVID-19 infection. The aim of this study was to reveal a possible association between the ABO-RH system and the risk of COVID-19 in the Moroccan population.

Materials and methods

This is an analytical cross-sectional study. It was carried out on 1094 patients for the diagnosis of Covid-19 by Rt-PCR at the Moulay Ismaïl military hospital in the province of Meknes. All Rt-PCR negative individuals were used as a comparison group.

Results

Among the 1094 individuals who were diagnosed, RT-PCR for detection of SARS-CoV-2 was positive for 242 individuals. Comparison of the proportions of blood groups of the two groups showed that the proportion of blood group A in patients with COVID-19 was significantly higher than in people in the comparison group (P = 0.007), while the proportion of blood group O in patients with COVID-19 was significantly lower than in people in the control group (P = 0.017). Comparison of the Rh blood groups of the two groups did not find a significant association (P = 0.608).

Conclusion

As demonstrated by several previous studies, we concluded that blood group A was associated with a higher risk of acquiring COVID-19. Equally, the O blood group was associated with a lower risk of infection.
Computational estimates of mitral annular diameter in systole and diastole cardiac cycle reveal novel genetic determinants of valve function and disease
Authors: Yu Mengyao , Tcheandjieu Catherine , Georges Adrien , Xiao Ke , Tejeda Helio , Dina Christian , Le Tourneau Thierry , Fiterau Ina ,   Regeneron Genetics Center, Judy Renae , Tsao Noah , Amgalan Dulguun , Munger Chad J , Engreitz Jesse M , Damrauer Scott , Bouatia-Naji Nabila , Priest James R.
Published: December 2020

The fibrous annulus of the mitral valve defines the functional orifice and anchors the anterior and posterior leaflets, playing an important role in normal cardiovascular physiology and valvular function. We derived automated estimates of mitral valve annular diameter in the 4-chamber view from 32,220 MRI images from the UK Biobank at ventricular systole and diastole as the basis for genome wide association studies. Mitral annular dimensions correspond to previously described anatomical norms and GWAS inclusive of four population strata identify ten loci, including novel loci (GOSR2, ERBB4, MCTP2, MCPH1) and genes related to cardiac contractility (BAG3, TTN, RBFOX1). ATAC-seq of primary mitral valve tissue localize multiple variants to regions of open chromatin in biologically relevant cell types and rs17608766 to an algorithmically predicted enhancer element in GOSR2. We observed strong genetic correlation with measures of contractility and mitral valve disease, and clinical correlations with heart failure, cerebrovascular disease, and ventricular arrythmias. A polygenic score of mitral valve annular diameter in systole was predictive of risk mitral valve prolapse across four cohorts (Odds ratio 1.19 per SD increase in polygenic score, 95% confidence interval 1.14 to 1.24, p=4.9E-11). In summary genetic and clinical studies of mitral valve annular diameter reveal new genetic determinants of mitral valve biology while highlighting known and previously unrecognized clinical associations. Polygenic determinants of mitral valve annular diameter may represent an independent risk-factor for mitral prolapse. Overall, computationally estimated phenotypes derived at scale from medical imaging represent an important substrate for genetic discovery and clinical risk prediction.
The influence of human genetic variation on Epstein-Barr virus sequence diversity
Authors: Rüeger Sina , Hammer Christian , Loetscher Alexis , McLaren Paul J , Lawless Dylan , Naret Olivier , Depledge Daniel P. , Morfopoulou Sofia , Breuer Judith , Zdobnov Evgeny , Fellay Jacques ,   Swiss HIV Cohort Study
Published: December 2020

Epstein-Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4+ T cell count <200/mm3 and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.
Can serum biomarkers predict the outcome of systemic therapy for atopic dermatitis?
Authors: Hurault Guillem , Roekevisch Evelien , Schram Mandy E. , Szegedi Krisztina , Kezic Sanja , Middelkamp-Hup Maritza A. , Spuls Phyllis I. , Tanaka Reiko J.
Published: December 2020

Background

Atopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification, rather than the “one-size-fits-all” treatments, is of high clinical relevance. It has been hypothesised that the measurement of biomarkers could help predict therapeutic response for individual patients.

Objective

We aim to assess whether biomarkers can predict the outcome of systemic therapy.

Methods

We developed a statistical machine learning predictive model using the data of an already published longitudinal study of 42 patients who received systemic therapy. The data contained 26 serum cytokines measured before the therapy. The model described the dynamics of the latent disease severity and measurement errors to predict AD severity scores (EASI, (o)SCORAD and POEM) two-weeks ahead. We conducted feature selection to identify the most important biomarkers for predicting the AD severity scores.

Results

We validated our model and confirmed that it outperformed standard time-series forecasting models. Adding biomarkers did not improve predictive performance. Our estimates of the minimum detectable change for the AD severity scores were larger than already published estimates of the minimal clinically important difference.

Conclusions

Biomarkers had a negligible and non-significant effect for predicting the future AD severity scores and the outcome of the systemic therapy. Instead, a historical record of severity scores provides rich and insightful dynamical information required for prediction of therapeutic responses.
Childhood growth and development and DNA methylation age in mid-life
Authors: Maddock Jane , Castillo-Fernandez Juan , Wong Andrew , Ploubidis George B , Kuh Diana , Bell Jordana T , Hardy Rebecca
Published: December 2020

Background

In the first study of its kind, we examine the association between growth and development in early life and DNAm age biomarkers in mid-life.

Methods

Participants were from the Medical Research Council National Survey of Health and Development(n=1,376). Four DNAm age acceleration(AgeAccel) biomarkers were measured when participants were aged 53y:AgeAccelHannum, AgeAccelHorvath, AgeAccelLevine and AgeAccelGrim. Exposure variables included relative weight gain (standardised residuals from models of current weight z-score on current height, and previous weight and height z-scores) and linear growth (standardised residuals from models of current height z-score on previous height and weight z-scores) during infancy (0-2y, weight gain only), early childhood(2-4y), middle childhood(4-7y) and late childhood to adolescence(7- 15y), age at menarche and pubertal stage for men at 14-15y. The relationship between relative weight gain and linear growth and AgeAccel was investigated using conditional growth models. We replicated analyses from the late childhood to adolescence period and pubertal timing among 240 participants from The National Child and Development Study(NCDS).

Results

A 1 SD increase in relative weight gain in late childhood to adolescence was associated with 0.50y(95% CI:0.20,0.79) higher AgeAccelGrim. This was replicated in NCDS (0.57y(95%CI:-0.01, 1.16). A I SD increase in linear growth during early childhood was associated with lower AgeAccelLevine(−0.39y [95% CI:-0.74,-0.04) however we did not have the data to replicate this finding in NCDS. There was no strong evidence that relative weight gain and linear growth in childhood was associated with any other AgeAccel biomarker. There was no relationship between pubertal timing in men and AgeAccel biomarkers. Women who reached menarche ≥12y had 1.20y(95% CI:0.15,2.24) higher AgeAccelGrim on average than women who reached menarche <12y; however this was not replicated in NCDS.

Conclusions

Our findings generally do not support an association between growth and AgeAccel biomarkers in mid-life. However, rapid weight gain during pubertal development, which we found to be related to older AgeAccelGrim and had previously been related to higher cardiovascular disease risk, warrants further investigation.
Causative Organisms, Antibiotic Sensitivity Patterns and Risk Factors Associated with Neonatal Sepsis at Moi Teaching and Referral Hospital, Kenya
Authors: Ateka Benard Mageto , Songok Julia , Nyandiko Winstone
Published: December 2020

Background

Neonatal bacterial infections have been associated with rising antimicrobial resistance levels. This has led to increasing neonatal morbidity and mortality in poorly resourced health facilities located in low income countries. Local studies on neonatal antibiotic sensitivity patterns and its associated risk factors could inform empirical antibiotic therapy and hospital infection control strategies.

Purpose

The study aimed at determining the causative organisms, antibiotic sensitivity patterns and risk factors associated with neonatal sepsis at a tertiary teaching hospital in Western Kenya.

Materials and Methods

Cross-sectional study among neonates suspected to have sepsis and undergoing treatment at Moi Teaching and Referral Hospital (MTRH’s) newborn unit (NBU) between September 2017 and July 2018. Blood culture tests isolated bacteria and determined their antimicrobial sensitivity. Neonatal and maternal characteristics were obtained through medical chart reviews. Descriptive statistics, Pearson chi-square test of association and odds ratios were adopted.

Results

The study enrolled 141 neonates, majority (57.4%) of whom were female. The median gestational age and birth weight were 37 (IQR: 22-45) weeks and 2400g (IQR: 800 - 4700) respectively. Of the 151 bacterial isolates identified, 46.4% were Klebsiella spp. followed by Coagulate negative staphylococcus (CoNS) at 27.8%. Klebsiella spp. was sensitive to meropenem, amikacin and cefepime but resistant to ceftriaxone, gentamycin and cefotaxime. However, CoNS was sensitive to vancomycin and penicillin. Both the neonatal and maternal risk factors assessed were not associated with neonatal sepsis.

Conclusion

The main bacterial causes of neonatal sepsis were Klebsiella spp. and CoNS which were both sensitivity to meropenem and amikacin.
Electrocorticography and stereo EEG provide distinct measures of brain connectivity: Implications for network models
Authors: Bernabei John M. , Arnold T. Campbell , Shah Preya , Revell Andrew , Ong Ian Z. , Kini Lohith G. , Stein Joel M. , Shinohara Russell T. , Lucas Timothy H. , Davis Kathryn A. , Bassett Danielle S. , Litt Brian
Published: December 2020

Brain network models derived from graph theory have the potential to guide functional neurosurgery, and to improve rates of post-operative seizure freedom for patients with epilepsy. A barrier to applying these models clinically is that intracranial EEG electrode implantation strategies vary by center, region and country, from cortical grid & strip electrodes (ECoG), to purely stereotactic depth electrodes (SEEG), to a mixture of both. To determine whether models derived from one type of study are broadly applicable to others, we investigate the differences in brain networks mapped by ECoG and SEEG in a cohort of patients who underwent surgery for temporal lobe epilepsy and achieved a favorable outcome. We show that networks derived from ECoG and SEEG define distinct relationships between resected and spared tissue, which may be driven by sampling bias of temporal depth electrodes in patients with predominantly cortical grids. We propose a method of correcting for the effect of internodal distance that is specific to electrode type and explore how additional methods for spatially correcting for sampling bias affect network models. Ultimately, we find that smaller surgical targets tend to have lower connectivity with respect to the surrounding network, challenging notions that abnormal connectivity in the epileptogenic zone is typically high. Our findings suggest that effectively applying computational models to localize epileptic networks requires accounting for the effects of spatial sampling, particularly when analyzing both ECoG and SEEG recordings in the same cohort, and that future network studies of epilepsy surgery should also account for differences in focality between resection and ablation. We propose that these findings are broadly relevant to intracranial EEG network modeling in epilepsy and an important step in translating them clinically into patient care.

Author summary

Bernabei et al. report that electrocorticography and stereo EEG provide different quantifications of epileptogenic zone connectivity due to differences in electrode type and implant patterns. After correcting for sampling differences between modalities, they find that more focal forms of epilepsy surgery target regions of weaker connectivity compared to the remaining epileptic network.
Determinants of COVID-19 Incidence and Mortality in the US: Spatial Analysis
Authors: Kathe Niranjan J. , Wani Rajvi J.
Published: December 2020

OBJECTIVES

The US continues to account for the highest proportion of the global Coronavirus Disease-2019 (COVID-19) cases and deaths. Currently, it is important to contextualize the spread and success of mitigation efforts. The objective of this study was to assess the ecological determinants (policy, health behaviors, socio-economic, physical environment, and clinical care) of COVID-19 incidence and mortality in the US.

METHODS

Data from the New York Times’ COVID-19 repository (01/21/2020-10/27/2020), 2020 County Health Rankings, 2016 County Presidential Election Returns, and 2018-2019 Area Health Resource File were used. County-level logged incidence and mortality rate/million were modeled using the Spatial Autoregressive Combined model and spatial lag model.

RESULTS

Counties with higher proportions of racial minorities (African American β= 0.007, Native Americans β= 0.008, Hispanics β= 0.015), non-English speakers (β= 0.010), population density ([logged] β= 0.028), and air pollution (β= 0.062) were significantly associated with high COVID-19 incidence rates. Subsequently, counties with higher Republican voters (β= 0.017), excessive drinkers (β= 0.107), children in single-parent households (β= 0.018), uninsured adults (β= 0.038), racial minorities (African American β= 0.032, Native Americans β= 0.034, Hispanics β= 0.037), females (β= 0.101), and population density ([logged] β= 0.270), air pollution (β= 0.130), and non-Whites/Whites’ residential segregation (β= 0.014) were significantly associated with high COVID-19 mortality rates. Additionally, longer state-level restrictions were associated with lower COVID-19 incidence and mortality rates.

CONCLUSIONS

The spatial models identified longer state-level restrictions, population density, air pollution, uninsured rate, and race/ethnicity as important determinants of the geographic disparities in COVID-19 incidence and mortality.
The impact of seasonal respiratory virus transmission on syndromic surveillance for COVID-19 in Ontario, Canada
Authors: Maharaj Arjuna , Parker Jennifer , Hopkins Jessica P. , Gournis Effie , Bogoch Isaac I. , Rader Benjamin , Astley Christina M. , Ivers Noah , Hawkins Jared B. , Tuite Ashleigh R. , Fisman David N. , Brownstein John S. , Lapointe-Shaw Lauren
Published: December 2020

Background

Syndromic surveillance systems for COVID-19 are being increasingly used to track and predict outbreaks of confirmed cases. Seasonal circulating respiratory viruses share syndromic overlap with COVID-19, and it is unknown how they will impact the performance of syndromic surveillance tools. Here we investigated the role of non-SARS-CoV-2 respiratory virus test positivity on COVID-19 two independent syndromic surveillance systems in Ontario, Canada.

Methods

We compared the weekly number of reported COVID-19 cases reported in the province of Ontario against two syndromic surveillance metrics: 1) the proportion of respondents with a self-reported COVID-like illness (CLI) from COVID Near You (CNY) and 2) the proportion of emergency department visits for upper respiratory conditions from the Acute Care Enhanced Surveillance (ACES) system. Separately, we plotted the percent positivity for other seasonal respiratory viruses over the same time period and reported Pearson’s correlation coefficients before and after the uncoupling of syndromic tools to COVID-19 cases.

Results

There were strong positive correlations of both CLI and ED visits for upper respiratory causes with COVID-19 cases up to and including a rise in entero/rhinovirus (r = 0.86 and 0.87, respectively). There was a strong negative correlation of both CLI and ED visits for upper respiratory causes with COVID-19 cases (r = −0.85 and −0.91, respectively) during a fall in entero/rhinovirus.

Interpretation

Two methods of syndromic surveillance showed strong positive correlations with COVID-19 confirmed case counts before and during a rise in circulating entero/rhinovirus. However, as positivity for enterovirus/rhinovirus fell in late September 2020, syndromic signals became uncoupled from COVID-19 cases and instead tracked the fall in entero/rhinovirus. This finding provides proof-of-principle that regional transmission of seasonal respiratory viruses may complicate the interpretation of COVID-19 surveillance data. It is imperative that surveillance systems incorporate other respiratory virus testing data in order to more accurately track and forecast COVID-19 disease activity.
Modelling the Test, Trace and Quarantine Strategy to Control the COVID-19 Epidemic in the State of São Paulo, Brazil
Authors: Amaku Marcos , Covas Dimas Tadeu , Coutinho Francisco Antonio Bezerra , Azevedo Neto Raymundo Soares , Struchiner Claudio , Wilder-Smith Annelies , Massad Eduardo
Published: December 2020

Testing for detecting the infection by SARS-CoV-2 is the bridge between the lockdown and the opening of society. In this paper we modelled and simulated a test-trace-and-quarantine strategy to control the COVID-19 outbreak in the State of São Paulo, Brasil. The State of São Paulo failed to adopt an effective social distancing strategy, reaching at most 59% in late March and started to relax the measures in late June, dropping to 41% in 08 August. Therefore, São Paulo relies heavily on a massive testing strategy in the attempt to control the epidemic.

Two alternative strategies combined with economic evaluations were simulated. One strategy included indiscriminately testing the entire population of the State, reaching more than 40 million people at a maximum cost of 2.25 billion USD, that would reduce the total number of cases by the end of 2020 by 90%. The second strategy investigated testing only symptomatic cases and their immediate contacts – this strategy reached a maximum cost of 150 million USD but also reduced the number of cases by 90%.

The conclusion is that if the State of São Paulo had decided to adopt the simulated strategy on April the 1st, it would have been possible to reduce the total number of cases by 90% at a cost of 2.25 billion US dollars for the indiscriminate strategy but at a much smaller cost of 125 million US dollars for the selective testing of symptomatic cases and their contacts.
Mapping each pre-existing condition’s association to short-term and long-term COVID-19 complications
Authors: Venkatakrishnan AJ , Pawlowski Colin , Zemmour David , Hughes Travis , Anand Akash , Berner Gabriela , Kayal Nikhil , Puranik Arjun , Conrad Ian , Bade Sairam , Barve Rakesh , Sinha Purushottam , O’Horo John C. , Badley Andrew D. , Soundararajan Venky
Published: December 2020

Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage 1.1 million clinical notes from 1,903 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0-30 days, 31-60 days, and 61-90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (23% of 383 complications) followed by cardiac arrhythmia (12% of 383 complications). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia and anemia. Furthermore, novel associations between cancer (risk ratio: 3, p=0.02) or immunosuppression (risk ratio: 4.3, p=0.04) with early-onset heart failure have also been identified. Onset of new complications after 30 days is rare and most commonly involves pleural effusion (31-60 days: 24% of 45 patients, 61-90 days: 25% of 36 patients). Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways.
Anemia is a risk factor for rehospitalization after SARS-CoV-2 clearance
Authors: Lenehan Patrick , Ramudu Eshwan , Venkatakrishnan AJ , Berner Gabriela , McMurry Reid , O’Horo John C. , Badley Andrew D. , Morice William , Halamka John , Soundararajan Venky
Published: December 2020

Background

As the number of new and recovering COVID-19 cases continues to rise, it has become evident that patients can experience symptoms and complications after viral clearance. Clinical biomarkers characterizing patients who are likely to experience these prolonged effects are unknown.

Methods

We conducted a retrospective study to compare longitudinal lab test measurements (hemoglobin, hematocrit, estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen) in patients rehospitalized after PCR-confirmed SARS-CoV-2 clearance (n=104) versus patients not rehospitalized after viral clearance (n=278).

Findings

Compared to patients who were not rehospitalized after PCR-confirmed viral clearance, those who were rehospitalized had lower median hemoglobin levels in the year prior to COVID-19 diagnosis (cohen’s D = -0.50; p=1.2×10−3) and during the active infection window (cohen’s D = -0.71; p=4.6×10−8). Patients hospitalized after viral clearance were also more likely to be diagnosed with moderate or severe anemia during the active infection window (OR = 2.18; p = 4.99×10−9).

Conclusions

The occurrence of moderate or severe anemia in hospitalized COVID-19 patients is strongly associated with rehospitalization after viral clearance. Whether interventions to mitigate anemia can improve long term outcomes of COVID-19 patients should be further investigated.

Funding

This study was funded by nference.
A Systematic Review and Meta-Analysis of Studies Examining the Relationship Between Reported Racism and Health and Wellbeing for Children and Adolescents
Authors: Priest Naomi , Doery Kate , Truong Mandy , Guo Shuaijun , Trenerry Brigid , Karlsen Saffron , Kelly Yvonne , Paradies Yin
Published: December 2020

Introduction

There is a growing body of research showing associations between experiences of racism and poor health and wellbeing outcomes for children and adolescents. The aim of this review protocol is to update the first systematic review conducted by Priest et al. 2013, including a meta-analysis of findings. Based on previous empirical data, it is anticipated that child and adolescent health will be negatively impacted by racism. This review will provide updated evidence of effect sizes across outcomes and identify moderators and mediators of relationships.

Methods and analysis

This systematic review and meta-analysis will include studies that explore associations between experiences of racism and racial dissemination with health outcomes of children and adolescents aged 0- 24 years of age from any racial/ethnic/cultural group. Outcome measures include general health and wellbeing, physical health, mental health, healthcare utilisation and health behaviours. Exposure measures include self- reported and proxy reported personal experiences of racism and reported experiences of vicarious racism. The authors will conduct a comprehensive search of studies from the earliest time available to September 2020. All relevant studies will be screened with data extraction, quality appraisal and publication bias conducted independently by at least two authors.

Ethics and Dissemination

This review will provide evidence for future research within the field and help to support policy and practice development. Results from this systematic review and meta-analysis will be widely disseminated to both academic and non-academic audiences.

Ethics approval is not required as this is a review of existing empirical findings.

Article Summary

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This is an updated systematic review which aims to update the findings from the first international review conducted by Priest et al. 2013. However, it is the first meta-analysis to be conducted exploring the relationship between racism and health in child and adolescent from all ethnic/racial/cultural backgrounds.

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This systematic review will show the health effects of racial discrimination on child and adolescent health, the key pathways by which racial discrimination influences these outcomes and identify potential moderators and mediators.

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Findings from this systematic review and meta-analysis will be used to provide recommendations for future research and inform the development of effective evidence-based strategies for addressing racism and ameliorating its harmful effects.

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This systematic review has a bias towards papers published in English as this review will only search studies published in English, meaning that studies not-published in English will not be included in this review. By doing so this review may not include all findings of all relevant studies.
First annotated draft genomes of non-marine ostracods (Ostracoda, Crustacea) with different reproductive modes
Authors: Van Patrick Tran , Anselmetti Yoann , Bast Jens , Dumas Zoé , Galtier Nicolas , Jaron Kamil S. , Martens Koen , Parker Darren J. , Robinson-Rechavi Marc , Schwander Tanja , Simion Paul , Schön Isa
Published: December 2020

ABSTRACTS

Ostracods are one of the oldest crustacean groups with an excellent fossil record and high importance for phylogenetic analyses but genome resources for this class are still lacking. We have successfully assembled and annotated the first reference genomes for three species of non-marine ostracods; two with obligate sexual reproduction (Cyprideis torosaandNotodromas monacha) and the putative ancient asexualDarwinula stevensoni. This kind of genomic research has so far been impeded by the small size of most ostracods and the absence of genetic resources such as linkage maps or BAC libraries that were available for other crustaceans. For genome assembly, we used an Illumina-based sequencing technology, resulting in assemblies of similar sizes for the three species (335-382Mb) and with scaffold numbers and their N50 (19-56 kb) in the same orders of magnitude. Gene annotations were guided by transcriptome data from each species. The three assemblies are relatively complete with BUSCO scores of 92-96%, and thus exceed the quality of several other published crustacean genomes obtained with similar techniques. The number of predicted genes (13,771-17,776) is in the same range as Branchiopoda genomes but lower than in most malacostracan genomes. These three reference genomes from non-marine ostracods provide the urgently needed basis to further develop ostracods as models for evolutionary and ecological research.
Efficacy of lysophosphatidylcholine as direct treatment in combination with colistin againstAcinetobacter baumanniiin murine severe infections models
Authors: Miró-Canturri A , Ayerbe-Algaba R , Jiménez-Mejías ME , Pachón J , Smani Y
Published: December 2020

Objectives

The stimulation of the immune response to prevent the progression of the infection may be an adjuvant to antimicrobial treatment. Previously, we showed that preemptive treatment with lysophosphatidylcholine (LPC) in combination with colistin improved the therapeutic efficacy of colistin against MDRAcinetobacter baumannii. In this study, we aimed to evaluate the efficacy of direct treatment with LPC in combination with colistin in murine experimental models of severe infections byA. baumannii.

Methods

We usedA. baumanniistrain Ab9, which is susceptible to colistin and most of the antibiotics used in clinical settings, andA. baumanniistrain Ab186, which is susceptible to colistin but presents a MDR pattern. The therapeutic efficacies of one and two doses of LPC (25 mg/kg/d) and colistin (20 mg/kg/8h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models.

Results

One and two doses of LPC in combination with colistin and colistin monotherapy enhanced bacterial clearance of Ab9 and Ab186 from spleen, lungs and blood and reduced mortality rates compared with those of the non-treated mice group in both experimental models (P<0.05). Moreover, one and two doses of LPC reduced the bacterial concentration in tissues and blood in both models, and increased mice survival in peritoneal sepsis model for both strains compared with those of colistin monotherapy group.

Conclusions

LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the infection by MDRA. baumannii.
Free testosterone and malignant melanoma risk in men: prospective analyses of testosterone and SHBG with 19 cancers in men and postmenopausal women UK Biobank
Authors: Watts Eleanor L. , Perez-Cornago Aurora , Knuppel Anika , Tsilidis Konstantinos K. , Key Timothy J. , Travis Ruth C.
Published: December 2020

We investigated the associations of estimated free and total circulating testosterone and sex hormone-binding globulin (SHBG) with cancer risk in men and postmenopausal women, using a pan-cancer approach, including 19 cancers in UK Biobank.

Risk was estimated using multivariable-adjusted Cox regression in up to 182,608 men and 122,112 postmenopausal women who were cancer-free at baseline. Participants diagnosed with cancer within two years of baseline were excluded. Hazard ratios (HRs) and confidence intervals (CIs) were corrected for regression dilution bias using repeat measurements. We accounted for multiple testing using the false discovery rate.

In men, higher free testosterone was associated with higher risks of melanoma and prostate cancer (HR per 50 pmol/L increase=1.35, 95% CI 1.14-1.61 and 1.10,1.04-1.18, respectively). Higher total testosterone was associated with an elevated risk of liver cancer (HR per 5 nmol/L=2.45,1.56-3.84), and higher SHBG was associated with a higher risk of liver cancer (HR per 10 nmol/L=1.56,1.31-1.87) and a lower risk of prostate cancer (0.93,0.91-0.96); associations with liver cancer were attenuated after excluding early follow-up. In postmenopausal women, higher free and total testosterone and lower SHBG were associated with elevated risks of endometrial (HR per 10 pmol/L=1.59,1.32-1.90; HR per 0.5 nmol/L=1.34,1.18-1.52 and HR per 25 nmol/L=0.78,0.67-0.91, respectively) and breast cancer (1.32,1.22-1.43;1.24,1.17-1.31 and 0.88,0.83-0.94, respectively).

We report a novel association of free testosterone with malignant melanoma in men; our findings also support known associations between sex hormones and risks for prostate, breast and endometrial cancers. The association with liver cancer in men may be attributable to reverse causation.
Cortical Mechanisms of Visual Hypersensitivity in Women at Risk for Chronic Pelvic Pain
Authors: Kmiecik Matthew J. , Tu Frank F. , Silton Rebecca L. , Dillane Katlyn E. , Roth Genevieve E. , Harte Steven E. , Hellman Kevin M.
Published: December 2020

Multisensory hypersensitivity (MSH), which refers to persistent discomfort across sensory modalities, is a risk factor for chronic pain. Developing a better understanding of the neural contributions of disparate sensory systems to MSH may clarify its role in the development of chronic pain. We recruited a cohort of women (n=147) enriched with participants with menstrual pain at risk for developing chronic pain. Visual sensitivity was measured using a periodic pattern-reversal stimulus during EEG. Self-reported visual unpleasantness ratings were also recorded. Bladder pain sensitivity was evaluated with an experimental bladder-filling task associated with early clinical symptoms of chronic pelvic pain. Visual stimulation induced unpleasantness was associated with bladder pain and evoked primary visual cortex excitation; however, the relationship between unpleasantness and cortical excitation was moderated by bladder pain. Thus, future studies aimed at reversing the progression of MSH into chronic pain should prioritize targeting of cortical mechanisms responsible for maladaptive sensory input integration.
ENDOTHELIAL CELL-DERIVED EXTRACELLULAR VESICLES ELICIT NEUTROPHIL DEPLOYMENT FROM THE SPLEEN FOLLOWING ACUTE MYOCARDIAL INFARCTION
Authors: Akbar Naveed , Braithwaite Adam , Corr Emma , Koelwyn Graeme , van Solingen Coen , Cochain Clement , Saliba Antoine-Emmanuel , Corbin Alastair , Pezzolla Daniela , Edgar Laurienne , Gunadasa-Rohling Mala , Banerjee Abhirup , Paget Daan , Lee Charlotte , Hogg Eleanor , Costin Adam , Dhaliwal Raman , Johnson Errin , Krausgruber Thomas , Riepsaame Joey , Melling Genevieve , Shanmuganathan Mayooran , Acute Myocardial Infarction Study Oxford , Bock Christoph , Carter David , Channon Keith , Riley Paul , Udalova Irina , Moore Kathryn , Anthony Daniel , Choudhury Robin
Published: December 2020

Acute myocardial infarction rapidly increases blood neutrophils (<2 hours). Release of neutrophils from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 hours after injury, and after neutrophil elevation. This suggests that additional non chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 minutes) release of extracellular vesicles (EVs), which are enriched in vascular cell adhesion molecule-1 (VCAM-1) and miRNA-126, and are thus a potential mechanism for communicating with remote tissues.
Here, we show that injury to the myocardium rapidly mobilises neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to their arrival at injured tissue. Ischemic myocardium leads to the generation and release of EC-derived-EVs bearing VCAM-1. EC-EV delivery to the spleen alters inflammatory gene and chemokine protein expression, and mobilises neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing we generated VCAM-1-deficient EV and showed that its deletion removed the ability of EC-EV to provoke the mobilisation of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model. Our findings show a novel mechanism for the rapid mobilisation of neutrophils to peripheral blood from a splenic reserve, independent of classical chemokine signalling, and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells.
Why simple face masks are unexpectedly efficient in reducing viral aerosol transmissions
Authors: Freitag Steffen , Howell Steven G. , Jim Kevin T. C.
Published: December 2020

During the current pandemic and in the past, shortages of high quality respirators have forced people to protect themselves with homemade face masks that filter poorly in comparison to N95 respirators 1–4 and are often designed in ways that makes them susceptible to leaks 5,6. Nevertheless, there is compelling epidemiological 7,8 and laboratory evidence 9–12 that face masks can be effective in impeding the spread of respiratory viruses such as influenza and SARS-CoV-2. Here we show that this apparent inconsistency can be resolved with a simple face mask model that combines our filtration efficiency measurements of various mask materials with existing data on exhaled aerosol characteristics. By reanalyzing these data we are able to reconcile the vastly different aerosol size distributions reported 13–19 and derive representative volume distributions for speech and breath aerosol. Multiplying filtration efficiency by those aerosol volumes, which are proportional to emitted viral load, shows that electrostatically charged materials perform the best but that even most uncharged fabrics remove > 85 % of breath and > 99 % of speech aerosol volume for exhaled particles < 10 µm in diameter. A leak model we develop shows the best uncharged fabric masks are made of highly air-permeable and often thin materials reducing viral load by up to 45 % and 50 % for breath and speech, respectively. Less permeable materials provide reduced protection because unfiltered air is forced through the leak. This can even render some charged materials inferior to uncharged household materials. Our model also shows that thin fabric masks provide protection for the wearer from aerosols expelled by another person reducing inhaled viral load by up to 20 % and 50 % and if leaks are avoided up to 35 % and 90 % for breath and speech, respectively.
Isolation and Characterization of Human Adipocyte-derived Extracellular Vesicles Using Filtration and Ultracentrifugation
Authors: Akbar Naveed , Pinnick Katherine E. , Paget Daan , Choudhury Robin P.
Published: December 2020

Extracellular vesicles (EVs) are lipid enclosed envelopes that carry biologically active material such as proteins, RNA, metabolites and lipids. EVs can modulate the cellular status of other cells locally in tissue microenvironments or through liberation into peripheral blood. Adipocyte- derived EVs are elevated in the peripheral blood and show alterations in their cargo (RNA and protein) during metabolic disturbances including, obesity and diabetes. Adipocyte-derived EVs can regulate the cellular status of neighboring vascular cells, such as endothelial cells and adipose tissue resident macrophages to promote adipose tissue inflammation. Investigating alterations in adipocyte-derived EVs in vivo is complex because EVs derived from peripheral blood are highly heterogenous and contain EVs from other sources, namely platelets, endothelial cells, erythrocytes and muscle. Therefore, the culture of human adipocytes provides a model system for the study of adipocyte derived EVs. Here, we provide a detailed protocol for the extraction of total small EVs from cell culture media of human gluteal and abdominal adipocytes using filtration and ultracentrifugation. We further demonstrate the use of Nanoparticle Tracking Analysis (NTA) for quantification of EV size and concentration and show the presence of EV-protein tumor susceptibility gene 101 (TSG101) in the gluteal and abdominal adipocyte derived-EVs. Isolated EVs from this protocol can be used for downstream analysis including, transmission electron microscopy, proteomics, metabolomics, small RNA-sequencing, microarray and utilized in functional in vitro/in vivo studies.

We describe the isolation of human adipocyte-derived extracellular vesicles (EVs) from gluteal and abdominal adipose tissue using filtration and ultracentrifugation. We characterize the isolated adipocyte-derived EVs by determining their size and concentration by Nanoparticle Tracking Analysis and by western blotting for the presence of EV-protein tumor susceptibility gene 101 (TSG101).
Systematic review and meta-analysis of the calibration of confidence judgments in individuals with schizophrenia spectrum disorders
Authors: Rouy Martin , Saliou Pauline , Nalborczyk Ladislas , Pereira Michael , Roux Paul , Faivre Nathan
Published: December 2020

Background

Metacognitive deficits are well documented in schizophrenia spectrum disorders as a decreased capacity to adjust confidence to first-order performance in a cognitive task. Because metacognitive ability directly depends on first-order performance, observed metacognitive deficits might be driven by lower first-order performance. We aimed to determine the extent to which individuals with schizophrenia experience specific deficits when producing confidence judgments and examined whether studies controlling for first-order performance found metacognitive deficits of smaller magnitude.

Method

Electronic databases were searched for studies published until April 24th2020. We conducted a Bayesian meta-analysis of 43 studies comparing the calibration of confidence in 1458 individuals with schizophrenia compared to 1337 matched controls. Group analyses and meta-regressions quantified how metacognitive deficits depended on task performance, cognitive domains, clinical severity, and antipsychotic dosage.

Outcomes

We found a global metacognitive deficit in schizophrenia (g = -0.57, 95% CrI [-0.71, -0.43]), which was driven by studies which did not equate first-order performance between groups (g = -0.64, 95% CrI [-0.77, -0.51]), and inconclusive among controlled-studies (g = -0.28, 95% CrI [-0.63, 0.07], BF01= 1.3). Plus, the metacognitive deficit in non-controlled studies was correlated with first-order performance. No correlation was found between metacognitive deficit and clinical features of schizophrenia.

Interpretation

We provide evidence for the existence of a deficit in the calibration of confidence judgments in schizophrenia, which is inflated due to non-equated first-order performance. Thus, efforts should be made to develop experimental protocols accounting for lower first-order performance in schizophrenia.
Screening for SARS-CoV-2 infection in asymptomatic individuals using the Panbio™ COVID-19 Antigen Rapid Test (Abbott) compared to RT-qPCR
Authors: Winkel Beatrice M.F. , Schram Emma , Gremmels Hendrik , Debast Sylvia B. , Schuurman Rob , Wensing Annemarie M.J. , Bonten Marc J.M. , Goedhart Edwin , Hofstra L. Marije ,   Antigen Rapid Test Validation Group
Published: December 2020

Background

Antigen-based point of care tests for identification of SARS-CoV-2 may markedly enhance effectiveness of population-based controlling strategies. Previous studies have demonstrated acceptable sensitivity and high specificity compared to RT-qPCR in symptomatic individuals, but test performance for asymptomatic individuals is unknown.

Methods

Test performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) was compared to RT-qPCR in a longitudinal cohort study of asymptomatic football players and staff members of professional football clubs. Based on timing of symptoms and prior and subsequent test results, positive RT-qPCR tests were categorized as pre-symptomatic, early or late infection or persistent RNA shedding.

Findings

2425 tests were performed in 824 individuals, of which 52 (6.3%) were SARS-CoV-2 positive based on RT-qPCR. There were 2406 paired sets from asymptomatic subjects for analysis. Sixteen Panbio™ tests were inconclusive, for which sensitivity analyses were performed (considering results as either positive or negative or being excluded). Sensitivity of Panbio™ ranged from 61.76% (95% CI 49.2-73.3) to 69.12% (95% CI: 56.7-79.8) and specificity from 99.53% (95% CI: 99.2-99.8) to 100% (95% CI: 99.8-100). Sensitivity of Panbio™ to detect subjects with pre-symptomatic/early infection (n= 42) ranged from 81.82% (95% CI: 67.3-91.8) to 90.91% (95% CI: 78.3-97.5) with specificity always above 99%.

Interpretation

In asymptomatic subjects the Panbio™ COVID-19 Ag Rapid Test had sensitivity of 81.82% to 90.91% and specificity above 99% for identifying pre-symptomatic and early SARS-CoV-2 infection.

Funding

This study was funded by the executing institutes. The Panbio™ COVID-19 Ag Rapid Tests were provided by the Ministry of Health, Welfare and Sport (VWS).