Gender-specific effects of COVID-19 lockdowns on scientific publishing productivity: Impact and resilience

Available online 3 February 2023Rationale: The SARS-CoV2 pandemic led to drastic social restrictions globally. Early data suggest that women in science have been more adversely affected by these lockdowns than men, with relatively fewer scientific articles authored by women. However, these observations test broad populations with many potential causes of disparity. Australia presents a natural experimental condition where several states of similar demographics and disease impact had differing approaches in their social isolation strategies. The state of Victoria experienced 280 days of lockdowns from 2020 to 2021, whereas the comparable state of New South Wales experienced 107 days, most of these in 2021, and other states even fewer restrictions. Objective and methods: To assess how the gender balance changed in Australian biomedical publishing with the lockdowns, we created a custom workflow to analyse PubMed data from more than 120,000 published articles submitted in 2019–2021 from Australian authors. Results: Broadly, Australian women have been incredibly resilient to the challenges faced by the lockdowns. There was an increase in the number of published articles submitted in 2020 that was equally due to women as men, including from Victoria. On the other hand, articles specifically addressing COVID-19 were significantly less likely to be authored by women than those on other topics, a finding not likely due to particular gender imbalance in virology or viral epidemiology, since publications on HIV followed similar patterns to previous years. By 2021, this imbalance had reversed, with more COVID-19-related papers authored by women than men. Conclusions: These data suggest women from Victoria were less able to rapidly transition to new research early in the pandemic but had accommodated to the new conditions by 2021. This work indicates we need strategies to support women in science as the pandemic continues and to continue to monitor the situation for its impact on vulnerable groups.M. Ryan, J. Tuke, M.R. Hutchinson, S.J. Spence

The power of effective study design in animal Experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the realworld implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.R.A. Ankeny, A.L. Whittaker, M. Ryan, J. Boer, M. Plebanski, J. Tuke, S.J. Spence

Symptom extraction from the narratives of personal experiences with COVID-19 on Reddit

Social media discussion of COVID-19 provides a rich source of information into how the virus affects people’s lives that is qualitatively different from traditional public health datasets. When individuals self-report their experiences over the course of the virus on social media, it can allow for identification of the emotions each stage of symptoms engenders in the patient. Posts to the Reddit forum r/COVID19Positive contain first-hand accounts from COVID-19 positive patients, giving insight into personal struggles with the virus. These posts often feature a temporal structure indicating the number of days after developing symptoms the text refers to. This paper aims to quantify the change in discourse throughout a collective timeline of experiences being COVID-19 positive. We collected discourse in the form of Reddit posts from /r/COVID19Positive (4,610 posts from March 14th, 2020 to May 12th, 2020), and filter to capture stories from people who tested positive for COVID-19. We exploit the temporal structure exhibited in these diarised posts to obtain a collective timeline of experiences. Using topic modelling and sentiment analysis, we quantify the change in discussion of COVID19 throughout individuals’ experiences for the first 14 days since symptom onset. Discourse on early symptoms such as fever, cough, and sore throat was concentrated towards the beginning of the timeline, while language indicating breathing issues peaked around ten days after developing symptoms. Some conversation around critical cases was also identified and appeared at a roughly constant rate. We identified two clear clusters of positive and negative emotions associated with the evolution of these symptoms and mapped their relationships. Our results provide a perspective on the patient experience of COVID-19 that complements other medical data streams and can potentially reveal when mental health issues might appear.Curtis Murray, Lewis Mitchell, Simon Tuke, Mark Macka

Tacrolimus dose, blood concentrations and acute nephrotoxicity, but not CYP3A5/ABCB1 genetics, are associated with allograft tacrolimus concentrations in renal transplant recipients

First published: 01 March 2021AIM: Long-term use of the immunosuppressant tacrolimus is limited by nephrotoxicity. Following renal transplantation, the risk of nephrotoxicity may be determined more by allograft than by blood tacrolimus concentrations, and thus may be affected by donor CYP3A5 and ABCB1 genetics. Little is known regarding factors that determine tacrolimus intra-renal exposure. METHODS: This study investigated the relationship between trough blood (C0Blood ) and allograft (CGraft ) tacrolimus concentrations and tacrolimus dose, haematocrit, genetics, acute nephrotoxicity, rejection status, delayed graft function and time post-transplant. C0Blood and CGraft were quantified in 132 renal transplant recipients together with recipient and donor CYP3A5 (rs776746) and ABCB1 3435 (rs1045642) genotypes. RESULTS: C0Blood ranged from 2.6-52.3 ng/mL and CGraft from 33-828 pg/mg tissue. Adjusting for dose, recipients who were CYP3A5 expressors had lower C0Blood compared to non-expressors, whilst delayed graft function was associated with higher C0Blood . Linear regression showed that the significant predictors of CGraft were C0Blood (point-wise P = 7x10-10 ), dose (P = 0.004) and an interaction between C0Blood and acute tacrolimus nephrotoxicity (P = 0.0002), with an adjusted r2 = 0.35 and no contribution from donor or recipient CYP3A5 or ABCB1 genotype. The association between CGraft and acute nephrotoxicity depended on one very high CGraft (828 pg/mg tissue). CONCLUSIONS: Recipient and donor CYP3A5 and ABCB1 3435C>T genotypes are not determinants of allograft tacrolimus exposure in kidney transplant recipients. However, tacrolimus dose and C0Blood were significant predictors of CGraft , and the relationship between C0Blood and CGraft appeared to differ in the presence or absence of acute nephrotoxicity.Benedetta C. Sallustio, Benjamin D. Noll, Rong Hu, Daniel T. Barratt, Jonathan Tuke ... at al