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Abeysundara, Rasnitsyn, Fong et al. report that the presence of leptomeningeal metastatic tumour cells leads to the recruitment and remodelling of fibroblasts, which, in turn, facilitate the colonization and outgrowth of medulloblastoma cells in the leptomeninges.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

The oligometastasis hypothesis suggests certain metastases are limited in extent and curable with focal therapies. Here they identify three integrated molecular subtypes of colorectal cancer liver metastasis, which complement clinical risk stratification to distinguish the subset of oligometastatic patients.

By combining strategies in material design and advanced microfabrication, three-dimensional integrated stretchable electronic devices can be created, including an eight-channel sensing system with Bluetooth communication capabilities that can be used to extract an array of signals from the human body.

A chronically implanted biocompatible electrochemical microsensor allows long-term recording of subsecond dopamine dynamics in vivo. The microsensor can reliably detect behaviorally evoked dopamine release from dopamine neurons in the brain over a period of months in rats.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Paul Boutros, Robert Bristow and colleagues report a molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer. They find that multifocal tumors are highly heterogeneous, and they identify a novel recurrent amplification of MYCL1.

Studies of gene expression in lung cancer have the potential to affect patient care, but the general applicability of the derived classifiers is unclear. David Beer and his colleagues now analyze more than 400 lung tumors from subjects at six institutions using eight different classifiers and show that the combination of molecular and clinical data best predicts patient survival (pages 812–813).

Subsets of ILC3s upregulate the immunoregulatory checkpoint molecule CTLA-4 after stimulation in a microbiota-dependent manner, and advances to support CTLA-4⁺ ILC3s may represent a treatment opportunity in IL-23-driven chronic inflammation.

Broadly neutralizing antibodies (bNAbs) neutralize HIV-1 and exert Fc-dependent activities against infected cells. Here, Dufloo et al. show that bNAbs also block HIV-1 release by trapping viral particles at the surface of infected cells.

A major goal in neuropharmacology is to develop new tools to effectively test the therapeutic potential of pharmacological agents to treat neurological and psychiatric conditions. Here, authors present an in vivo drug screening system that generates large-scale brain activity maps to be used with machine learning to predict the therapeutic potential of clinically relevant drug leads.

CD4⁺ T cells are critical for the development of lymphedema. Here the authors show how these cells contribute to lymphedema and identify that the sphingosine-1-phosphate receptor modulator FTY720 can prevent lymphedema in a mouse tail injury model by blocking the release of CD4⁺ T cells from the lymph nodes to the skin.

Munc18-1 is an evolutionary conserved gene whose mutations are linked to various neurological diseases in human. In order to better understand the exact nature of the mutations, the authors here utilize several model systems to show mutant Munc18-1 can aggregate and deplete functional pool of Wt protein, and that chemical chaperones can reverse the cellular deficits.

Microscopy artifacts and tissue imperfections interfere with single-cell analysis. CyLinter software offers quality control for high-plex tissue profiling by removing artifactual cells, thereby facilitating accuracy of biological interpretation.

Crohn’s disease (CD) is a complex disease associated with immune dysregulation. Here the authors use multimodal data to identify and characterize an epithelial cell population, termed ‘LND’ cells, in both terminal ileum and ascending colon, with LND interacting locally with immune cells and potentially contributing to CD pathology.

New research indicates that the microbiota at many sites in the body, including the urinary tract, might influence urological health. Whiteside et al. review our current knowledge on the microbiome–host relationship and examine its role in the maintenance of urinary homeostasis, its utility as a predictor of the risk of disease and as a basis for the development of novel therapeutic strategies.

Activated B cell enter germinal centers (GC) to become plasma cells and memory B cells. Here the authors show that some memory B cells recycle to GC via CCL-21 mediated chemotaxis to deliver antigens from the lymph node subcapsular sinus (SCS) to potentially contribute to affinity maturation and antigenic drift.

In this Review, Teoh et al. describe different mechanisms of early and late disease recurrence in non-muscle-invasive bladder cancer and discuss potential treatment options. In addition, the authors discuss the potential of molecular classification and treatment with immunotherapy and novel therapeutic agents in the future management of bladder cancer.

Agnihotri and colleagues show that loss of the MAT2A enzyme of the methionine cycle induces a global depletion of H3K36me3 and extends survival in glioma models, representing a potential therapeutic vulnerability.

The quality of the chemical starting points for small-molecule drug discovery is a key factor in improving the likelihood of clinical success. In this article, experts from several organizations involved in drug discovery for malaria, tuberculosis and neglected tropical diseases present disease-specific criteria for hits and leads, and discuss the underlying rationale.

Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

Capturing radioactive organic iodides from nuclear waste is important for safe nuclear energy usage, but remains a significant challenge. Here, Li and co-workers fabricate a stable metal–organic framework functionalized with tertiary amine groups that exhibits high capacities for radioactive organic iodides uptake.

Zou et al. show that SMARCD3 regulates DAB1 activity and Reelin signalling in the developing cerebellum, which can be hijacked to promote medulloblastoma cell migration and metastatic dissemination.

Novel antimalarial drugs are urgently needed to combat parasite drug resistance. Here, Vaidya et al. describe a new chemical class of potent antimalarial compounds that act by disrupting the parasite's sodium homeostasis.

In this Review, Tonkin and Jordan draw on their clinical experience to discuss the etiology, diagnosis and management of distal anterior urethral stricture disease. They highlight that curative open surgery, such as graft or flap urethroplasty, should be preferred over repeated minimally invasive procedures in order to optimize patient outcomes.

Cleaved and intact type I collagen have different effects on pancreatic ductal adenocarcinoma (PDAC), and remodelling of type I collagen—mediated through DDR1 signalling—is a prognostic indicator for the survival of patients with PDAC.

ILC3s expressing MHC class II control the fate of inflammatory versus tolerogenic T cells that respond to the microbiota by selecting for antigen-specific RORγt⁺ T_reg cells and against T_H17 cells, establishing intestinal homoeostasis.

Relatively little is known about the first hematopoietic stem and progenitor cells to arrive in the fetal bone marrow. Here they characterize the frequency, function, and molecular identity of fetal BM HSPCs and their bone marrow niche, and show that most BM HSPCs have little hematopoietic function until birth.

Derailed differentiation of human-specific progenitors of the developing cerebellar rhombic lip is the cause of group 4 medulloblastoma, the most common childhood brain tumour. 

Climate anxiety, reflecting concerns about the negative impacts of climate change, is growing. Planning and action on individual specific climate risks could be a way to reduce personal climate anxiety.

The separation of C6 alkane isomers is crucial to the petroleum refining industry, but the distillation methods in place are energy intensive. Here, the authors design a series of topologically-guided zirconium-based metal-organic frameworks with optimized pore structures for efficient C6 alkane isomer separations.

A mapping approach that screens mutants in a sterile interspecific hybrid identifies the genetic determinants of differences in high-temperature growth between divergent Saccharomyces cerevisiae and Saccharomyces paradoxus yeast species.

The International Childhood Cancer Outcome Project group, involving survivors and other relevant stakeholders, develop a set of core outcomes to measure the quality of care for 17 types of childhood cancers.

A selective inhibitor of the kinetoplastid proteasome (GNF6702) is identified that is highly efficacious in vivo, clearing the parasites that cause leishmaniasis, Chagas disease and sleeping sickness from mice, highlighting the possibility of developing a single class of drugs for these neglected diseases.

Can traditional computational analysis and machine learning help compensate for inadequate peer review of drug-repurposing papers in the context of an infodemic?

The rise of drug resistance presents a significant challenge in the treatment of infectious diseases. This Review summarizes the status and mechanisms of drug resistance in malaria, human immunodeficiency virus (HIV) infection and tuberculosis, and explores strategies to address resistance that could be incorporated into drug development across these disease areas.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

Disease risk and treatment response is determined by an individual's complex history of genetic and environmental interactions. Personalized health care therefore requires an in-depth understanding of patient biology that can now be measured using '-omics' technologies. In this Review, different metabolic profiling methods and applications are described that might introduce a new dimension in personalized patient care in gastroenterology and hepatology.