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Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Immune checkpoint blockade can result in good outcomes in patients with metastatic head and neck squamous cell carcinoma (HNSCC), but not those with locally advanced disease. Here, the authors demonstrate that the addition of anti-NKG2A and anti-PD-L1 blockade to ATR inhibition and radiotherapy in the adjuvant setting can induce a robust antitumour immune response in mice.

The use of additives in the fabrication of solution-processed n-type perovskite transistors alleviates lattice strain and suppresses undercoordinated lead, boosting the charge transport properties of the devices and making them suitable for use in complementary circuit applications.

Epidemiological analyses coupled with immunological phenotyping suggest that humoral immunity induced by COVID-19 vaccines wanes more rapidly in individuals with severe obesity compared to individuals with a BMI within the normal range.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Howard Chang, Ravindra Majeti and colleagues define the chromatin accessibility and transcriptional landscapes in 13 human primary blood cell types and in acute myeloid leukemia cells. They identify potential regulators governing hematopoietic differentiation and genetic elements linked to regulatory evolution in cancer cells.

Low-cost point-of-care sensors are vital for precision medicine. Here, the authors have repurposed a glucometer for breast cancer therapeutic detection capable of sensing tamoxifen in human blood, utilizing blood glucose to power and amplify the therapeutic signals

AAV vectors form difficult-to-detect concatemers at Cas9 target sites.

The spike protein of the Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 than Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic and vaccine-elicited neutralizing antibodies.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

Diagnosis of rare, unpredictable, drug-induced liver injury (DILI) is a significant challenge for patients, clinicians, and drug development. Here, the authors discover, evaluate, and validate potential blood biomarkers to diagnose DILI and distinguish it from alternative causes of liver injury.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains challenging. Here, the authors show that endothelial-specific AAVs with serotype flexibility enable redosing and transform the brain vasculature into an in vivo biofactory in genetically diverse rodents. In primates, these vectors cross the blood-brain-barrier and show broad tropism.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Macrophages alter their metabolism in response to infection. The authors show that resting macrophages generate nicotinamide adenine dinucleotide via de novo synthesis, but activated and aged cells suppress the rate-limiting enzyme quinolinate phosphoribosyltransferase to regulate mitochondrial and immunological functions.

Analysing the regulatory consequences of mutations and splice variants at large scale in cancer requires efficient computational tools. Here, the authors develop RegTools, a software package that can identify splice-associated variants from large-scale genomics and transcriptomics data with efficiency and flexibility.

A new genome editing strategy can normalize the β-globin:α-globin balance in human hematopoietic stem cells from patients with β-thalassemia and restore functional adult hemoglobin tetramers in patient-derived red blood cells.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Chronic stress induces skeletal muscle atrophy via upregulation of glucocorticoid levels. Here, the authors show that SIRT6 transcriptionally regulates glucocorticoid-induced muscle atrophy by modulating IGF/PI3K/AKT signalling.

Recent evidence indicates that successful cancer clones must have overcome programmed cell removal. In this Opinion article, the authors explore the role of programmed cell removal in both normal and neoplastic cells.

The huntingtin protein (HTT) contains a polyQ tract preceded by an N-terminal flanking sequence (HTT^NT) that contributes to HTT aggregation. Now the role of HTT^NT in aggregation is explored in vitro, revealing a complex, multistep pathway initiated when polyQ disrupts HTT^NT structure, enhancing the latter's assembly into prefibrillar aggregates. Within these intermediates, subsequent interactions of the polyQ moieties drive further assembly into compact amyloid aggregates.

The chromatin-modifying protein SIRT6 has previously been shown to have anti-aging properties. Sundaresan et al. now show that SIRT6 expression is low in failing human hearts and SIRT6 in mice protects the heart by suppressing the activity of the c-Jun transcription factor, which acts as a global regulator of genes encoding components of the IGF-Akt signaling pathway.

A fluorescently labelled inhibitor of the DNA repair enzyme poly(ADP–ribose) polymerase 1 is used to detect epithelial cancers of the upper intestinal tract in animals, in biopsied human tissue and in a human patient.

Mitochondrial complex II is normally composed of four subunits. Here the authors show that bioenergetic stress conditions give rise to a partially assembled variant of complex II, which shifts the anabolic pathways to less energy demanding processes.

Comparisons of a chimeric recombinant version of SARS-CoV-2, the ancestral SARS-CoV-2 strain and an Omicron isolate show that the attenuated virulence of Omicron is caused by mutations in both the spike protein and nsp6.

Heligmosomoides polygyrus can activate mammalian TGF-β signalling pathways, but how it does so is not known. Here the authors identify and isolate a H. polygyrus TFG-β mimic that can bind both mammalian TGF-β receptor subunits, activate Smad signalling and generate inducible regulatory T cells.

These preclinical studies outline a CRISPR-based methodology for correcting β-globin gene mutations in haematopoietic stem cells to advance the development of next-generation therapies for β-haemoglobinopathies.

The delivery of therapeutics using an external trigger is an attractive route for the improvement of targeted disease treatment. Here, the authors have discovered a porphyrin–phospholipid liposome for light-controlled membrane permeabilization and use the system to deliver an anticancer drug in vivo.

Developing simple and efficient table-top sources of intense terahertz radiation is an ongoing pursuit. Here, Dey et al. demonstrate broadband terahertz generation from laser filamentation in liquids with an order of magnitude higher energy than from conventional two-color filamentation in air.

Piddock and colleagues explore new antibacterial compounds in active late discovery phase and preclinical development focusing on innovative strategies, with a global health perspective.

Exome analysis of chemical-carcinogen-induced mouse tumours provides evidence for T-cell-mediated immunoselection as a mechanism of immunoediting.

Heterologous expression of engineered gas vesicles allows noninvasive, deep-tissue ultrasound visualization of engineered bacteria in vivo in mouse tumour models and in the gastrointestinal tract.

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The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.