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CD123 expression on leukemic stem and progenitor cells (LSPCs) and leukemic blasts representing a promising therapeutic target. However previous CD123-targeting approaches had limited efficacy and safety concerns. The authors here evaluate the bispecific CD123/CD16A innate cell engager AFM28 and manifest its efficacy both in vitro and in vivo, which is mediated by NK cells.

Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.

Brown adipose cells contribute to body temperature maintenance by converting lipids and glucose into heat, and can be found in white adipose tissue. Wolfrum and colleagues find a population of cells in white adipose tissue that can adopt brown or white characteristics in response to cold.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Alveolar rhabdomyosarcoma is a clinically challenging disease due to the lack of druggable targets. Here the authors show preclinical evidence for ATR inhibitors as a therapeutic option for alveolar rhabdomyosarcoma.

Meshworks of claudin polymers control the paracellular transport and barrier properties of epithelial tight junctions. Here, the authors show different claudin nanoscale organization principles, finding that claudin segregation enables barrier formation and paracellular ion flux across tight junctions.

Exploratory post hoc analysis of molecular residual disease from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR-mutated stage IB–IIIA non-small-cell lung cancer shows that molecular residual disease detection predicts disease recurrence with long-term adjuvant osimertinib treatment.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Andre Franke and colleagues perform an association study of atopic dermatitis based on high-density genotyping using the Immunochip array. They identify four new susceptibility loci for this common inflammatory skin disease.

In the non-randomized phase 3b/4 DESTINY-Breast12 study, trastuzumab deruxtecan (T-DXd) treatment of patients with HER2⁺ advanced breast cancer and active or stable brain metastases showed consistent intracranial activity and systemic efficacy of T-DXd.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

The heterogeneity of colorectal cancer has important clinical and therapeutic implications. Here the authors analysed the responses of a large biobank of organoids and xenografts derived from colorectal patients to a panel of clinically relevant therapeutic agents to identify genes signatures associated with drug response.

An extensive RNA binding protein atlas (RBPome) for primary T cells would be a useful resource. Here the authors use two different methods to characterise the mouse and human T cell RBPome and show regulation of Roquin-1/2 dependent and independent pathways.

Acquired resistance to immunomodulatory drugs is common in multiple myeloma patients, but rarely attributed to genetic alterations. Here, proteomic, phosphoproteomic and RNA sequencing analysis in five paired pre-treatment and relapse samples reveals a CDK6-regulated protein resistance signature.

The heart forms from combining the first with the second heart field, which in mammals creates left and right ventricle. Here transgenic zebrafish and physiology studies reveal that transcription factors controlling septation in mammals already in teleosts guide muscle coupling by controlling the relative contribution of the two fields to the heart.

For molecular magnets and qubits, coupling between vibrations and electronic spins has a strong influence on spin state lifetime. Here, Kragskow et al present direct measurements of the vibronic transitions in a molecular magnet, showing the critical role of an “envelope effect” in the spectra.

Felix Stickel and colleagues report the results of a genome-wide association study of alcohol-related cirrhosis. They confirm PNPLA3 as a susceptibility locus and identify new association signals in MBOAT7 and TM6SF2.

The molecular mechanisms underlying cardiac chamber formation are not well understood. Here, the authors show that planar cell polarity signalling through Wnt5b and Wnt11 coordinates localised and tissue-scale polarised actomyosin contractility in the zebrafish heart, regulating cardiac chamber formation and looping.

ADAM17 is a member of the ‘Disintegrin and Metalloproteinase’ family of proteases, that cleaves transmembrane substrates from the surfaces of cells. Here the authors show that surface exposure of phosphatidylserine is required for ADAM17 sheddase activity, possibly by directing the protease to its substrates.

Functional T cell exhaustion occurs during chronic viral infection or in tumor settings. Beyer et al. report that chronic inflammation mediated by the cytokine TNF is responsible for this dysfunction and that blockade of this pathway restores immune system–mediated control of viral infection.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

The beetle Tribolium castaneum is a commonly used laboratory model, combining the ease of systematic RNAi experiments like those in Caenorhabditis elegans, with biology that is more representative of most insects than Drosophila melanogaster. A large consortium has sequenced and analysed the genome of the red flour beetle, creating a resource for biologists everywhere.

Wickström and colleagues describe how mechanical forces applied to epidermal stem cells lead to relocation of emerin to the nuclear envelope and reduced nuclear actin levels, resulting in chromatin changes that influence lineage commitment.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Interferon-γ acts on tumour endothelial cells to drive vascular regression, inducing ischaemia that leads to tumour collapse.

Lenk et al find that the preB cell receptor (preBCR) is associated with infiltration and relapse of acute lymphoblastic leukemia in the central nervous system (CNS). They also show that downregulation of preBCR component CD79a reduces the engraftment of leukemia cells in different murine xenograft models, particularly in the CNS.

Transcranial electrical stimulation (tES) can be used in combination with functional MRI (fMRI) to study brain functions. This Consensus Statement provides a checklist for reporting concurrent tES-fMRI research.

Young-Ae Lee and colleagues report results of a genome-wide association study for atopic dermatitis. They identify a risk locus on chromosome 11q13 in a region previously associated with risk of Crohn's disease.

Compared with other medical imaging techniques, ultrasonography is inexpensive, safe, and increasingly valuable. Nevertheless, its use is—so far—recommended in only one preliminary classification criteria. As this situation looks set to change rapidly, this Review provides an overview of the use of ultrasonography in rheumatology, both now and in future.

Superconducting hybrid systems are becoming an increasingly important platform to conduct investigations in the field of quantum information processing. Here, the authors report a highly cooperative coupling between the nuclear spin of an Yb(III) molecular complex with a superconducting microwave resonator achieving a large hyperfine-mediated coupling between a resonator mode and the nuclear spin that could be used for the realization and readout of qudits.