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Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here authors demonstrate that in a mouse model for recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them, suggesting treatment modalities for deafness may require restoration of the function of both hair cells and neurons.

Eos is a newly discovered molecular cloud sitting just 94 pc from the Sun. It was detected through the far-UV emission of its molecular hydrogen, having been missed in conventional molecular gas surveys due to a low abundance of common gas tracers.

The conduction electron and magnon interactions are essential for the understanding and development of spintronics and superconductivity. Here the authors show a deep binding energy kink in spin-resolved photoemission spectra which is understood as a signature the many-body spin flip excitation in Fe single crystal thin film.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

It is currently thought that visual pigments in vertebrate photoreceptors are regenerated exclusively through enzymatic cycles. Here the authors show that mammalian photoreceptors also regenerate opsin pigments in light through photoisomerization of N-ret-PE (N-retinylidene-phosphatidylethanolamine.

Immunostimulatory antibodies have strong potential as anti-cancer therapeutics. Here Elliott et al. show that conformational rigidity determines agonistic activity of antibodies targeting CD40 and 4-1BB and demonstrate further enhancement of agonism through disulfide engineering.

Quantum light sources operating at telecom wavelength are a long-sought goal for quantum technologies. Here, the authors show electrically injected emission of single photons and entangled photon pairs from indium phosphide based quantum dots, operating up to a temperature of 93 K.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

A technique that combines retrograde axon tracing with single-cell transcriptomics is used to characterize neurons innervating pancreatic ductal adenocarcinoma and healthy pancreas, providing insight into the role of neural connections in cancer progression.

In quantum optical technologies, identical emitters of indistinguishable single photons are difficult to realize due to the inherent dissimilarity of each emitting device. Here, Rogers et al.demonstrate a solid-state uniform single-photon source, which does not require external tuning of optical properties.

Induced pluripotent stem cells (iPSCs) hold great potential for modelling human developmental processes and diseases. Here the authors induce human iPSCs to spontaneously form fully laminated three-dimensional retinal tissue containing functional photoreceptor cells.

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps .

Cancer cells enriched in cholesterol in their plasma membrane impair T-cell-mediated cytotoxicity, which can be augmented by stiffening the cancer cells via cholesterol depletion, as shown in mouse models of adoptive T-cell immunotherapy.

The layered material α-RuCl₃ is a promising candidate for the Kitaev quantum spin liquid, but its low-temperature structure is debated. Here, using a new structural characterization approach, the authors report a pressure-induced high-symmetry phase in α-RuCl₃, which might be close to the ideal Kitaev geometry.

In the non-randomized phase 3b/4 DESTINY-Breast12 study, trastuzumab deruxtecan (T-DXd) treatment of patients with HER2⁺ advanced breast cancer and active or stable brain metastases showed consistent intracranial activity and systemic efficacy of T-DXd.

Keyl et al. present an explainable artificial intelligence model-based real-world data analysis from over 15,000 patients across 38 cancer types, identified key prognostic marker interactions, and confirmed these in an external lung cancer cohort.

It has been previously shown that combining immune checkpoint inhibitors with TGFβ blockade potentiates anti-tumor immune responses. Here the authors show that, in an immune excluded preclinical tumor model, combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8 + T cells.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

Bacillus anthracis causes the infectious disease anthrax. Here, the authors synthesized deoxy glycosides that are effective against B. anthracis and related bacteria and found that these amphiphilic compounds kill bacteria via an unusual mechanism of action.

By leveraging diverse datasets from brain stimulation therapy for Tourette Syndrome and tic-inducing brain lesions, Baldermann et al. reveal a critical role of action-related functional networks in both the treatment and pathophysiology of tic disorders.

The organic material κ-H₃(Cat-EDT-TTF)₂ has been suggested to exhibit a quantum spin liquid phase in which quantum fluctuations prevent the formation of magnetic order. Here, the authors show that this may be a result of fluctuations of hydrogen atoms, rather than more conventional geometric frustration.

Nitrogen depletion in the ocean provides a favourable niche for nitrogen-fixing cyanobacteria, which can form symbioses with eukaryotic algae. This study reports the discovery of two distinct marine pennate diatom–diazotroph symbioses, which had previously only been observed in freshwater environments and represent an overlooked but widespread source of bioavailable nitrogen in marine habitats.

Food biodiversity is likely to benefit both human health and agrifood systems. To assess food biodiversity, this epidemiological study proposes the use of dietary species richness, which is highly heterogeneous—both between and within countries—and is associated with lower rates of mortality in Europe and similar levels of micronutrient adequacy in low- and middle-income countries, as opposed to other classical indices.

Retinal pigment epithelium (RPE) plays an important role in diabetic retinopathy (DR) progression. Here, the authors show AKT1 and AKT2 are reciprocally regulated in the RPE of DR donor tissue and diabetic mice, reducing Akt2 in RPE causing a compensatory increase in Akt1 and attenuating DR.

The synthesis of molecular nanostructures often requires the variation of several parameters, such as stoichiometry, pH, counter-ion etc. Here, the authors report a flow reaction array with algorithmic control which is used as a ‘search engine’ to isolate six nanoscale clusters from a massive parameter space.

The authors present the largest genome-wide association study to date for a rare Parkinsonian disorder, progressive supranuclear palsy (PSP). They include follow-up investigations of the identified susceptibility loci, functional consequences, and cell-specific pathologies, providing insights into genetic and molecular mechanisms underlying PSP.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Age-related macular degeneration (AMD) has been connected to deficits in autophagy. Here, the authors demonstrate, in mice and dry-AMD patient samples, that calcium and integrin binding protein 2 (CIB2) regulates Rheb-mTORC1 signaling axis, and subsequently autophagy.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Quantum communication networks would greatly benefit from the possibility to have solid-state emitters being directly interfaced with telecom fibers, without the need for wavelength conversion. Here, the authors demonstrate coherent control of an InAs/InP quantum dot, as well as entanglement between its electron spin and the frequency of a telecom photon.

SARS-CoV-2 mutations associated with the escape from antibody-mediated neutralization have been widely reported. Here, in a patient with defective antibody responses, the authors find a potential association between SARS-CoV-2 mutations and CD8 T alterations to implicate possible contributions of CD8 T cells in evasion of SARS-CoV-2 from host immunity.

Pseudomonas aeruginosa-derived 2-nonyl-4-quinolone N-oxide exerts bactericidal effects on Neisseria gonorrhoea via zeta1–epsilon1 toxin–antitoxin activation in vitro and abrogates experimental infection in mice.

Replication initiation is stochastic and obscured in population sequencing; D-NAscent reports the use of long nanopore reads to detect base analogs and thus to assess replication initiation at the individual molecule level.

The oncogene MYC plays a key role in cancer initiation and progression. Using thousands of CRISPR perturbations, the authors investigate regulators of MYC in six different cancers. These tumor-specific regulators suggest potential therapeutic targets for this oncogene.

The accuracy of melanoma diagnosis can vary considerably among clinicians, impacting both patient outcomes and the performance of related AI tools. Here, the authors systematically assess interrater variability among expert pathologists reviewing histopathological images and clinical metadata of melanoma-suspicious lesions collected at eight German hospitals.

Due to the abundance of pathogenic variants in Peripherin-2, causing peripherin-2-associated inherited retinal disorders, and the lack of any approved treatment, it is imperative to identify an effective therapeutic strategy. Here the authors show that reducing rhodopsin levels improves retinal function and structure and decreases inflammatory responses.

CHIMERYS is a spectrum-centric and data acquisition method-agnostic algorithm for the analysis of MS2 spectra. It is capable of deconvoluting any MS2 spectrum, regardless of whether it was acquired by DDA, DIA or PRM, thus unifying the analysis of bottom-up proteomics data.