Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies.

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

Unlabelled: The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia.

Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a.

CD4 T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat.

Beyond compliance: harmonising research and husbandry practices to improve experimental reproducibility using fish models.

Reproducibility in animal research is impacted by the environment, by husbandry practices in the laboratory and by the animals' provenance. These factors, however, are often not adequately considered by researchers. A disconnect between researchers and animal care staff can result in inappropriate housing and husbandry decisions for scientific studies with those animals.

Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.

The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection.

A new approach to grant review assessments: score, then rank.

Background: In many grant review settings, proposals are selected for funding on the basis of summary statistics of review ratings. Challenges of this approach (including the presence of ties and unclear ordering of funding preference for proposals) could be mitigated if rankings such as top-k preferences or paired comparisons, which are local evaluations that enforce ordering across proposals, were also collected and incorporated in the analysis of review ratings. However, analyzing ratings and rankings simultaneously has not been done until recently.

Gender-based homophily in collaborations across a heterogeneous scholarly landscape.

In this article, we investigate the role of gender in collaboration patterns by analyzing gender-based homophily-the tendency for researchers to co-author with individuals of the same gender. We develop and apply novel methodology to the corpus of JSTOR articles, a broad scholarly landscape, which we analyze at various levels of granularity. Most notably, for a precise analysis of gender homophily, we develop methodology which explicitly accounts for the fact that the data comprises heterogeneous intellectual communities and that not all authorships are exchangeable.

Refinement: Measuring informativeness of ratings in the absence of a gold standard.

We propose a new metric for evaluating the informativeness of a set of ratings from a single rater on a given scale. Such evaluations are of interest when raters rate numerous comparable items on the same scale, as occurs in hiring, college admissions, and peer review. Our exposition takes the context of peer review, which involves univariate and multivariate cardinal ratings.

Improving zebrafish laboratory welfare and scientific research through understanding their natural history.

Globally, millions of zebrafish (Danio rerio) are used for scientific laboratory experiments for which researchers have a duty of care, with legal obligations to consider their welfare. Considering the growing use of the zebrafish as a vertebrate model for addressing a diverse range of scientific questions, optimising their laboratory conditions is of major importance for both welfare and improving scientific research. However, most guidelines for the care and breeding of zebrafish for research are concerned primarily with maximising production and minimising costs and pay little attention to the effects on welfare of the environments in which the fish are maintained, or how those conditions affect their scientific research.

NIH peer review: Criterion scores completely account for racial disparities in overall impact scores.

Previous research has found that funding disparities are driven by applications' final impact scores and that only a portion of the black/white funding gap can be explained by bibliometrics and topic choice. Using National Institutes of Health R01 applications for council years 2014-2016, we examine assigned reviewers' preliminary overall impact and criterion scores to evaluate whether racial disparities in impact scores can be explained by application and applicant characteristics. We hypothesize that differences in commensuration-the process of combining criterion scores into overall impact scores-disadvantage black applicants.

Effects of environmental enrichment on survivorship, growth, sex ratio and behaviour in laboratory maintained zebrafish Danio rerio.

Environmental enrichment involves increasing the complexity of a fish's environment in order to improve welfare. Researchers are legally obliged to consider the welfare of laboratory animals and poor welfare may result in less robust data in experimental science. Laboratory zebrafish Danio rerio are usually kept in bare aquaria for ease of husbandry and, despite being a well-studied species, little is known about how laboratory housing affects their welfare.