interferon beta-1b (Infibeta)

Correction: Deubiquitinase USP35 restrains STING-mediated interferon signaling in ovarian cancer.

Zhang Jiawen J, Chen Yunfei Y, Chen Xianfei X, Zhang Wen W et al.

Lost and found in translation: the value of the human imiquimod model.

Meijs Anouk C AC, van den Noort Juliette A JA, Assil Salma S, Klarenbeek Naomi B NB et al.

Topical imiquimod (IMQ), a Toll-like receptor (TLR) 7 agonist, induces transient cutaneous inflammation and is widely used in preclinical research as a 'psoriasis-like' mouse model. However, accumulating evidence indicates substantial divergence between IMQ-driven biology and human plaque psoriasis pathogenesis. To bridge this translational gap, we compare here the experimental conduct, readouts and mechanistic insights engaged by IMQ challenge in mice vs. healthy human participants. Importantly, molecular and cellular analyses indicate that IMQ predominantly activates interferon regulatory factor (IRF) signalling in humans, rather than NF-κB pathways as observed in animals. Moreover, differences in neutrophil response and complement activation were also identified. These discrepancies may reflect interspecies variation in TLR7 expression as well as methodological differences between the animal and human IMQ model. Despite certain limitations related to psoriasis translatability, the human IMQ model has demonstrated translational relevance in several early phase clinical trials. It represents a valuable tool for evaluating target engagement and characterizing downstream pharmacodynamic effects of novel compounds, particularly those targeting the TLR7-IRF-type I interferon axis. In conclusion, the human IMQ model can serve as valuable mechanistic model driving disease-related pathways, rather than as a proxy for plaque psoriasis disease biology. Fit-for-purpose benchmarking and method standardization are essential to maximize translational utility of the IMQ model.

Beta-lactam de-labelling as a core antimicrobial stewardship strategy in the era of the antimicrobial resistance pandemic: a narrative review.

Bhattacharya Sudip S, Kundu Soumi S

Antimicrobial resistance (AMR) is increasingly recognised as a global public health emergency that threatens the foundations of modern medicine. While much attention has focused on antimicrobial overuse, under-emphasised drivers such as inaccurate drug allergy labels continue to undermine antibiotic stewardship efforts. Beta-lactam allergy (BLA) labels, particularly penicillin allergy labels, are among the most prevalent and most consequential of these inaccuracies. Mounting evidence demonstrates that the vast majority of individuals labelled as beta-lactam allergic are not truly allergic, yet these labels persist across healthcare systems and generations, driving the use of broader-spectrum, less effective, more toxic and resistance-promoting antibiotics. In this timely review, we argue that beta-lactam de-labelling should no longer be viewed as a niche allergy intervention but as a core antimicrobial stewardship strategy and an ethical obligation in the era of the AMR pandemic. Drawing on emerging inpatient and outpatient evidence, including recent paediatric inpatient de-labelling studies, we examine clinical, behavioural, system-level and ethical barriers to de-labelling and propose a reframing of beta-lactam de-labelling as a public health intervention essential for preserving antibiotic effectiveness. We conclude by outlining policy-relevant recommendations for embedding de-labelling into routine care pathways, particularly in low and middle-income countries (LMICs), where the consequences of AMR are likely to be most severe.

Elevated Plasma Phospho-Tau217 in Beta-Propeller Protein-Associated Neurodegeneration.

Lee Jae-Hyeok JH, Kim Yun Soo YS