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Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

Nuclear quantum effects affect chemical processes and material properties. Here the authors use path-integral molecular dynamics simulation to analyze their effects on themophysical properties of 92 organic liquids across the chemical space.

Voltage-modulated scanning probe microscopy may elucidate important processes at solid–liquid interfaces, but it is complicated by the presence of mobile ions. By incorporating force sensitivity into a multidimensional measurement approach, Collins et al.present a technique that overcomes these limitations.

The formation of lithium dendrites on the metal electrode surface of lithium batteries can lead to short circuits, making them potentially unsafe and unusable. The use of in situ NMR spectroscopy provides time-resolved and quantitative information about the nature of metallic lithium deposited on lithium-metal electrodes.

How neural codes are passed from one brain area to the next remains poorly understood. Here, the authors show how neuronal feedback inhibition converts incoming temporal information into sparse rate information in a biophysical network model of the dentate gyrus.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Coventry et al. show that spatial demonstratives—such as ‘this’ and ‘that’ in English—are selected on the basis of whether the speaker is able to reach the object or not, across 29 diverse languages.

Spin-crossover materials are promising for caloric cooling, but their powder nature prevents exploring elastocaloric properties. Here, the authors propose spin-crossover polymer composites with giant elastocaloric effects.

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Here, the authors present a multinational study on the application of deep learning algorithms for COVID-19 diagnosis against multiple lung conditions as controls.

Flow limitation is exploited to develop a microfluidic device exhibiting flow–pressure behaviour analogous to the current–voltage characteristics of an electronic transistor.

THOC6 is required for TREX tetramer formation. Analysis of pathogenic THOC6 variants differentiate the conserved mRNA export functions of TREX dimers and RNA processing functions of TREX tetramers underlying THOC6 Intellectual Disability Syndrome.

Kubo et al. report two kindreds that exhibit a deficiency of iRHOM2, which interacts with ADAM17, leading to defective release of TNF and CD62L and resulting in altered immune responses to opportunistic infections.

HIV-1 infection in humans and SIV infection in rhesus macaques are associated with mucosal damage to the gastrointestinal tract, microbial translocation and chronic immune activation. Here the authors develop a non-human primate DSS colitis model that recapitulates these aspects of the disease in uninfected rhesus macaques.

CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth.

A conserved mechanism for the regulation of replisome disassembly in eukaryotes is shown using cryo-electron microscopy, revealing a role for DNA in the preservation of replisome integrity.

Brain region-specific oligodendrocyte population dynamics are unclear. Here the authors implement long-term in vivo three-photon imaging to determine those dynamics in the cortical and subcortical areas in the living intact and demyelinated adult mouse brain.

Plants immune responses are triggered upon perception of volatile monoterpenes. Here, Wenig et al. show that a feed-forward loop featuring LEGUME LECTIN-LIKE PROTEIN1 propagates monoterpene-associated cues both within and between plants, illustrating how systemic immunity could act at a population level.

Dysregulation of lung T_reg cell function contributes to asthma development. Chatila and colleagues find that allergens upregulate Notch4–Hippo–Wnt signaling in T_reg cells, triggering their release of GDF15 growth factor, which drives type 2 innate lymphoid cell activity and asthma.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

The spindle assembly checkpoint (SAC) safeguards chromosome segregation by regulating the anaphase promoting complex/cyclosome (APC/C), allowing chromosomes to correctly attach to mitotic spindles. Here the authors reveal a role for Cullin–RING ubiquitin ligase complex 4 (CRL4) in regulating metaphase to anaphase transition via BUB3 degradation.

FOXP3 deficiency leads to dramatic loss of immune homeostasis. This multicenter collaborative group finds that loss of FOXP3 function only disrupts a few core genes, but this unmasks a degree of systemic inflammation, and it is this environment that then strongly perturbs T_reg cells.

Cunningham et al. characterize the ubiquitin chain linkages regulated by the opposing activities of the E3 ligase parkin and the deubiquitylation enzyme USP30 on mitochondria.

METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) is the first effort to provide the burgeoning field of whole body-MRI (WB-MRI) with minimum standards of image acquisition, interpretation, and reporting; it should act as a catalyst for promoting the use of this promising method.

DNA replication processes are often dysregulated in cancer. Here the authors analyse DNA synthesis patterns in cancer cells undergoing partial genome re-replication to reveal that re-replication exhibits aberrant replication fork dynamics and a skewed distribution of replication initiation that over-duplicates early-replicating genomic regions.

Divergent transcription from promoters and enhancers occurs in many species, but it is unclear if it is a general feature of all eukaryotic cis regulatory elements. Here the authors define cis regulatory elements in worms, flies, and human; and identify several differences in regulatory architecture among metazoans.

RepID has previously been shown to promote origin firing. Here the authors reveal that RepID regulates replication origins via the recruitment of the CRL4 complex, and prevents re-initiation and unscheduled DNA replication.

Though high ionic thermopower and p-n conversion has been realized in liquid ionic thermoelectric materials, achieving similar performance in solid-state polymer materials remains a challenge. Here, the authors report all-solid-state thermoelectric polymer composites with tunable ionic thermopower.

The expression of two specific DNA-repair factors promotes homology-directed repair and enhances the precision of CRISPR–Cas9 gene editing at multiple loci in human cells, including patient-derived induced pluripotent stem cells.

Low magnesium mobility in solids represents a significant obstacle to the development of Mg intercalation batteries. Here the authors show that substantial magnesium ion mobility can be achieved in close-packed ternary selenide spinel materials.

Dock8 deficiency leads to defects in humoral immunity. Geha and colleagues show that Dock88 interacts with MyD88 to bridge TLR9 signaling to the Src-Syk-STAT3 pathway to promote B cell proliferation and differentiation.

MRI has become an established tool in the diagnosis, management and treatment of localized prostate cancer. However, standardized guidelines on reporting prostate MRI have not yet been developed. A recent consensus study proposes a certification framework for reporting prostate MRI in the UK.

For patients who present with localized prostate cancer, focal therapy could be a treatment option; however, accurate imaging of the prostate is required for focal therapy to be viable. This Review by Turkbey et al. discusses the conventional methods for imaging the prostate, the new developments for targeted imaging, and the possible role of image-guided biopsy and focal therapy.

The combination of conventional anatomical MRI and functional magnet resonance sequences–known as multiparametric MRI (mp-MRI) is emerging as an accurate tool for identifying clinically relevant tumours. This Review discusses the role of mp-MRI in the detection, staging, and treatment planning of prostate cancer.

In Cappadocia, Turkey, a mesothelioma epidemic causes 50% of all deaths in three small villages. This manuscript reports, from a personal viewpoint, the scientific advances that have come from studying the families who have an inherited predisposition to develop this disease and the social problems that they face.

Robert Graham and colleagues carried out a GWAS meta-analysis for Parkinson's disease (PD) and report 17 new risk loci. Their analyses support a key role for autophagy and lysosomal biology in PD risk.