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Flood management solutions are typically local and do not consider how the space–time connectivity of floods is exacerbated by built infrastructure. Through a case study of the 2014 flood in Southeast Michigan, which flooded where there was no rainfall, this Article examines key factors contributing to urban flooding and the implications of design choices on inundation.

Off-target activation of nerve fibers is an ongoing problem in bioelectronic medicines such as vagus nerve stimulation. Here, the authors show that high-frequency stimulation can selectively block nerve fibers in the vagus nerve in swine models.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.

Experimental demonstration of quantum speedup that scales with the system size is the goal of near-term quantum computing. Here, the authors demonstrate such scaling advantage for a D-Wave quantum annealer over analogous classical algorithms in simulations of frustrated quantum magnets.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Here the authors reveal how an incoherent feedforward C/EBPα–Notch circuit times lung cell fate, guiding alveolar development, repair after injury, and shifts between protective and reparative states.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Direct observation of G-quadruplexes (G4s) in live cells is challenging. Here the authors report a method to identify G4s within the nuclei of live and fixed cells using a fluorescent probe combined with fluorescence lifetime imaging microscopy.

De novo designed interleukin-4 mimetics were engineered that induce biased signaling activation and exhibit high thermal stability. These mimetics offer insight into cytokine signaling and can be directly incorporated into 3D-printed biomaterials

A set of tools maps tandem repeats across complete genomes.

The M₅ muscarinic acetylcholine receptor represents a promising therapeutic target for neurological disorders. Here, the authors reveal a 2.1 Å cryo-EM structure of the M₅ bound to a selective positive allosteric modulator site that enables structure-based drug design.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

This study reports on self-aggregating injectable microcrystals for administering long-acting drug implants via low-profile needles, a key factor in patient adoption. Microcrystal self-aggregation is engineered through a solvent exchange process to form depots with minimal polymer excipient, demonstrating enhanced long-term release of a model contraceptive drug in rodents.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Multi-Omic approaches are a powerful way for obtaining in-depth understanding of a cell’s state. Here the authors present DISCO, combining digital microfluidics, laser cell lysis, and artificial intelligence-driven image processing to analyze single-cell genomes, transcriptomes and proteomes in a mixed population.

Deficiency in NAD+ has been implicated in skeletal deformities during development in both humans and mice. Here, the authors use mice that lack the critical enzyme of the NAD+ salvage pathway Nampt in mesenchymal lineage cells to show that the NAD salvage pathway is indispensable for endochondral but not intramembranous bone development.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Ji et al. identify an idiopathic generalised epilepsy network that links heterogeneously distributed brain abnormalities to a common brain network and deep brain stimulation sites which reduce generalised seizures.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease.

Despite substantial investments in urban stormwater management systems around the world, cities are experiencing soaring impacts that are inconsistent with assumed levels of flood protection. This suggests that there are flaws in existing stormwater design methods and guidelines, which currently do not properly account for the complexity of flood flows in urban landscapes and their interactions with infrastructure and with natural and artificial water bodies.

Sports-related concussion is increasingly recognized as a potential danger to paediatric populations, but its short-term and long-term consequences remain poorly understood. This Expert Consensus Document is the result of a 1-day meeting convened by Safe Kids Worldwide, the Alzheimer's Drug Discovery Foundation, and the Andrews Institute for Orthopaedics and Sports Medicine, with the aim of highlighting knowledge gaps and areas of critically needed research in youth sports-related concussion.

HiFi genome sequencing accesses DNA methylation and nucleotide variation in long sequence reads. Here, the authors apply this approach in a rare disease cohort to identify DNA hypermethylation linked to genetic variants including rare disease alleles.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

Conditional genetic knockout is achieved in the rat by using zinc-finger nucleases to place loxP sites at specific genomic locations and introducing Cre recombinase under the control of a native promoter.

On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.

High-density integration will be vital for silicon photonics, but as we approach sub-wavelength distances between components, the crosstalk becomes intolerable. Here, Song et al. demonstrate waveguide integration at a half-wavelength pitch with low crosstalk using advanced superlattice design concepts.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

There are currently no validated methods for the diagnosis of prion disease at the preclinical stage. Here the authors show that serial protein misfolding cyclic amplification and real-time quaking-induced conversion can be used to detect prions in the skin of prion-inoculated hamsters and humanized transgenic mice at early preclinical stages.

A prostate cancer epigenome map reveals that genes are suppressed in clusters through long-range epigenetic silencing (LRES). Regions of LRES contain known tumour suppressors and miRNAs, and may expand to neighbouring genes during tumour progression.

Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

Inflammasomes are multiprotein complexes, including the protein ASC, that assemble in response to inflammatory stimulation. Here the authors characterise the regulation of ASC during inflammasome formation and show the involvement of SUMOylation and zinc-finger and BTB domain-containing protein 16 (ZBTB16).