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It remains unclear why some BRCA-deficient high-grade serous carcinomas (HGSC) do not respond to platinum-based therapy. Here, multi-omic analysis of BRCA1- and BRCA2-deficient HGSC attributes co-occurring mutations, DNA repair deficiency and tumor microenvironment features to short survival in these patients.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

A machine-learning model that integrates data from wearable devices (such as smartwatches) with blood biomarkers and demographic data can predict whether someone has insulin resistance, enabling timely lifestyle interventions to prevent progression to type 2 diabetes.

The use of chalcogenide glass in optical science and applications at the UV frequencies has been so far hindered by its absorption in this spectral region. Here the authors demonstrate that a nanostructured chalcogenide glass can efficiently generate third harmonic radiation, leading to a strong UV light source at the nanoscale.

Physical networks typically employ enthalpy-dominated crosslinking interactions that become more dynamic at elevated temperatures. Here, the authors report an entropy-driven physical network based on polymer-nanoparticle interactions that exhibits mechanical properties that are invariant with temperature.

Instabilities in chiral plasmas can amplify electromagnetic waves, raising the question of whether chiral solids behave similarly. Now a magneto-chiral instability is demonstrated in tellurium, observed as growing terahertz emission after photoexcitation.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The crystal structure of a 92,000 M_r fragment of yeast DNA topoisomerase II suggests how the enzyme can facilitate the passage of one segment of duplex DNA through a double-stranded break in another.

Long non-coding RNAs (lncRNAs) can contribute to cancers that are driven by Sonic hedgehog (SHH) signaling. Here the authors report that lncRNA HHIP-AS1 stabilises the mRNA of dynein complex 1, thereby, promoting the pro-mitotic effects of SHH-driven tumors.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Singlet fission may one day allow solar cells to produce two excited electrons with one photon. Now, by comparison of the time-resolved photoluminescence and sensitized triplet–triplet annihilation of a tetracene derivative, it has been shown that—contrary to previous reports—the excimer state is a trap, and not a necessary intermediate for singlet fission.

Ependymoma is a tumor of the brain or spinal cord with the two most common and aggressive types mainly occurring in children. Here the authors employ 3D genomics and epigenomics to reveal targets for aggressive ependymoma tumors in children.

Haploinsufficiency in three genes associated with risk of autism spectrum disorder—KMT5B, ARID1B and CHD8—in cell lines from multiple donors results in cell-type-specific asynchronous development of GABAergic neurons and cortical deep-layer excitatory projection neurons.

The Hubbard model describes the physics of strongly correlated electron systems, but is difficult to solve. Now, a scheme to systematically and efficiently relate the exactly solvable Hatsugai–Kohmoto model to the Hubbard model has been identified.

Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are challenging to diagnose, as they exhibit features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). Here, the authors use deep learning to re-classify cHCC-CCA tumours into HCC or ICCA based on histopathology images.

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.

Galsky and colleagues report the results of a phase 1 clinical trial of anti-programmed cell death protein 1 ligand 1 atezolizumab in combination with PGV001, a personalized neoantigen vaccine, in participants with urothelial cancer.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

A study using a mouse solid tumour model suggests that adjusting the dosing frequency of the PI3Kδ inhibitor AMG319 in the treatment of human cancers could decrease tumour growth with fewer adverse effects.

Diamond quantum magnetometry is utilized to directly read the vorticity of antiferromagnetic spin textures through coupled multi-polar emergent magnetic charge distributions.

Animal models of infection with Zika virus (ZIKV) are urgently needed for a better understanding of pathogenesis and for testing potential therapies. Here, the authors describe infection of rhesus macaques with an Asian-lineage ZIKV strain as a relevant animal model for studying ZIKV pathogenesis.

In this study, the authors use a maternal infection mouse model to show that Zika virus infection during pregnancy reshapes offspring immunity in a sex-specific manner, weakening neutrophil defenses and heightening vulnerability to infections and inflammation later in life.

The making of a multi-author book can be a long and frustrating business for all those involved — contributors, academic editor and publisher. Here Anthony Watkinson charts the sequence of events and describes what can go awry.

Plasmonics and metamaterials enable ptychographic coherent diffractive imaging with improved reconstructed phase and amplitude. The approach may be particularly useful for imaging of extremely thin or highly transparent objects.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Projections of future sea level rely on the understanding of the relationship between sea-level and past climate changes. This study reconstructs 30,000 years of sea level evolution along Atlantic Africa in response to the climatic modifications.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Dense three-dimensional integration of photonics and electronics results in a high-speed (800 Gb s⁻¹) data interface for semiconductor chips that features 80 communication channels and consumes only tens of femtojoules per transmitted bit.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

The conditions under which networks of neurons exhibit critical dynamics remains unclear. Here, the authors investigate how simple neural cultures reorganize activity when embodied in a gameplay environment and find that network wide neural criticality arises in nuanced ways.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

The fine interface between crystallinity and amorphicity in synthetic hybrid materials has to-date been relatively under-explored. Here, the authors probe the relationship between amorphisation and melting behaviour in zeolitic metal-organic frameworks as a route towards functional glasses.

Feske and colleagues show how STIM- and ORAI-dependent calcium activation of NFAT plus IFN–STAT1 signaling activates T-bet expression independently of IL-12 stimulation. This NFAT–STAT1 activation pathway is required for T_H1 cell differentiation and protection against viral infections when IL-12 is missing.

Comparison of association signals in UK Biobank using different strategies for assessing genetic variation shows that whole-exome sequencing combined with array genotyping and imputation offers similar performance to whole-genome sequencing at a reduced cost.

Three distinct families of gut bacteria encode an unprecedented number of respiratory-like reductases per genome to perform anaerobic respiration of biomedically relevant substrates.

Immunometabolic cues surrounding implanted biomaterials govern the trafficking of subsets of neutrophils, monocytes and other immune cells, and determine the relative composition of pro-inflammatory and anti-inflammatory immune cell populations.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Breast cancers are classified based on gene expression profiles but it is well known that DNA methylation patterns are also altered. Here the authors, by combining genome-wide DNA methylation and gene expression analysis, identify transcriptional networks regulated by DNA methylation at enhancers able to separate specific breast cancer subtypes.