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In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

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.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Sassano et al. identify endoplasmic reticulum–mitochondria contact sites as the intracellular location where phospholipid peroxidation first occurs to promote ferroptosis. Manipulating these contact sites dictates ferroptosis sensitivity in breast cancer.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

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.

Here, the authors present 74 radiocarbon and 31 luminescence age determinations from four sites in southern Italy. They use these data to suggest that Neanderthal disappearance in the region predated the appearance of early modern humans, a previously unclear chronology

Here the authors develop an assay capable of selecting Sec61 inhibitors by exploiting the inactivation of firefly luciferase, once translocated into the endoplasmic reticulum (ER), and the possibility of diverting and “re-lighting” luciferase into the cytosol by a Sec61 inhibitor.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

In systems with a persistent spin texture, spin polarization of states is unidirectional and independent of momentum, which reduces spin dissipation. This feature makes persistent spin textures attractive for spintronics, and here, Kilic and coauthors demonstrate that, with the exception of the trivial space group, P1, persistent spin textures are universally present in all nonmagnetic solids lacking inversion symmetry.

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.

NK cells play an important role in anti-tumour immunity, however, the immune-hostile microenvironment often impairs their function. Here authors show that cancers disable autophagy in NK cells, and by restoring this process, intra-tumour NK cells could be re-invigorated.

Tumor-associated macrophages are pivotal in control over solid tumors. Here the authors show that these macrophages express chemosensors that detect lipid variants in the tumor microenvironment that can regulate the function of these cells.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Levels of the metabolic coenzyme NAD⁺ decline during aging, which is linked to many age-related diseases. Zhang et al. review recent clinical and translational evidence testing NAD⁺ supplementation in age-related diseases, highlighting therapeutic challenges and opportunities.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

As quantum information processing continues to develop apace, the need for integrated photonic devices becomes ever greater for both fundamental measurements and technological applications. To this end, Crespiet al.demonstrate a high-fidelity photonic controlled-NOT gate on a glass chip.

Genome assembly of durum wheat cultivar Svevo enables genome-wide genetic diversity analyses highlighting modifications imposed by thousands of years of empirical selection and breeding.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

The assumption that light sources based on radiative cascades provide maximally polarization-entangled photons is not always correct. Here the authors show experimentally in cavity-embedded quantum dots that photon polarization correlates with its emission mode, impacting the degree of entanglement for emitted photon pairs.

Phylogenetic analysis is used to identify transmission chains, but no software is available for the automated partition of large phylogenies. Prosperiet al. apply a new search algorithm to identify transmission clusters within the phylogeny of HIV-1gene sequences linking molecular and epidemiological data.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

The homeostasis and function of adipose tissue are tightly regulated by immune cells, with macrophages playing a pivotal role. Here the authors show that PpargHIGH macrophages positively enhance brown adipose tissue thermogenesis through GDF15.

Double Asteroid Redirection Test (DART) mission’s impact on asteroid Dimorphos has led to various impact related features. Here, the authors show that those features result naturally from the dynamical interaction of the ejecta with the binary system and solar radiation pressure.

Short laser pulses of femtosecond time scales are in high demand in order to explore the fast electron dynamics in light-matter interactions. Here, the authors demonstrated the compression of free electron laser pulses in the extreme ultraviolet range by using a chirped pulse amplification technique.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRH^OB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

Rovito et al. conduct deep immune profiling of hospitalized and unvaccinated individuals with persistent symptoms three months post COVID-19. They explore the role of SARS-CoV-2 RNAemia and peripheral inflammation in driving immune dysregulation, finding impaired responses in the humoral arm partially linked to RNAemia.

Fiorina and colleagues document alterations in glucose metabolism in patients with COVID-19 and use continuous glucose monitoring to show that glycaemic abnormalities could still be detected 2 months after disease onset in patients who had recovered.

Colour code on a superconducting qubit quantum processor is demonstrated, reporting above-breakeven performance and logical error scaling with increased code size by a factor of 1.56 moving from distance-3 to distance-5 code.

X-ray polarimetry observations with the Imaging X-ray Polarimetry Explorer constrain the accretion geometry in an X-ray pulsar and provide evidence for a misalignment of the spin, magnetic and orbital axes in Her X-1.