CAR T-cell-associated secondary malignancies challenge current pharmacovigilance concepts.

Suspected adverse reactions following chimeric antigen receptor T-cell (CAR T) treatment include more and more cases of secondary T-cell malignancies. The causality assessment of such suspected reactions challenges established evaluation practices due to (i) patient and product-specific risk factors and (ii) incomplete data available with post-marketing reports submitted to competent authorities. This is of particular relevance for gene therapy products that integrate into the host genome.

Tralokinumab Treatment of Atopic Dermatits Induces A Progressive Transcriptomic Response.

Atopic dermatitis (AD) is characterized by a complex epidermal barrier deficiency and exaggerated immune responses dominated by type-2-mechanisms with variable contributions of additional immune axes. Interleukin (IL)-13 is overexpressed in AD skin and a key driver of both barrier dysfunction and inflammation. We here prospectively studied the effects of IL-13 inhibition with tralokinumab on cutaneous transcriptome profiles using RNA sequencing of biopsies from 16 moderate-to-severe AD patients obtained at baseline, week 2 and week 16.

SKA2 enhances stress-related glucocorticoid receptor signaling through FKBP4-FKBP5 interactions in neurons.

Genes involved in regulating the hypothalamic-pituitary-adrenal (HPA) axis, including the glucocorticoid receptor (GR), are linked to various stress-related psychopathologies including bipolar disorder as well as other mood and trauma-related disorders. The protein product of the cell cycle gene, is a GR interaction partner in peripheral cells. However, the precise roles of SKA2 in stress and GR signaling in the brain, specifically in nonreplicating postmitotic neurons, and its involvement in HPA axis regulation remain unclear.

Gatemon Qubit on a Germanium Quantum-Well Heterostructure.

Gatemons are superconducting qubits resembling transmons, with a gate-tunable semiconducting weak link as the Josephson element. Here, we report a gatemon device featuring an aluminum microwave circuit on a Ge/SiGe heterostructure embedding a Ge quantum well. Owing to the superconducting proximity effect, the high-mobility two-dimensional hole gas confined in this well provides a gate-tunable superconducting weak link between two Al contacts.