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What do people mean when they say their lives are meaningful? Hicks and colleagues suggest that experiential appreciation, or valuing and appreciating one’s experiences, represents a unique pathway to the subjective feeling that life is meaningful.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Giardini et al. present an imaging method that combines quantitative measurements of cardiac electrophysiology with high-resolution three-dimensional structural reconstructions, enabling the detection of arrhythmogenic electrical coupling between cardiomyocytes and non-myocytes in murine hearts.

As large-scale neurodevelopmental MRI studies gain prominence, the authors identify tradeoffs between sample size and quality control that can dramatically affect results, and they evaluate a range of approaches to mitigate risk for error.

The authors present a multicenter database to investigate the neural correlates of dreaming, including physiological, behavioral and experiential data. This database could boost the research on the mechanisms of dreaming in humans and the signatures of consciousness.

By integrating large-scale genomic and proteomic data in cerebrospinal fluid and plasma, the authors identify 49 proteins linked to MRI markers of cerebral small vessel disease, highlighting extracellular matrix and immune pathways, with biomarker and therapeutic potential.

Most genetic association studies have been done on single nucleotide polymorphisms and small indels, while other types of variants have been less studied. Here, the authors use whole genome sequencing in a diverse population to identify and provide experimental evidence for associations between structural variants and blood-cell traits.

Electronic health records are a rich source of clinical data but identifying associations with outcomes is complex. Here, the authors propose a modelling framework ‘InfEHR’ that identifies patient trajectories in electronic health records and generates a likelihood for clinical phenotypes.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

The transmission spectrum of the exoplanet WASP-39b is obtained using observations from the Single-Object Slitless Spectroscopy mode of the Near Infrared Imager and Slitless Spectrograph instrument aboard the JWST.

The warm Earth-sized planet LHS 475 b is validated and characterized with two transits observed by the JWST. The absence of evident spectroscopic features excludes a substantial hydrogen envelope and indicates that LHS 475 b has either little or no atmosphere or an optically thick cloud deck at high altitudes.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The authors find the human red nucleus is functionally connected with action and motivated behavior networks, instead of motor-effector networks. They argue the red nucleus implements goal-directed behavior, integrating behavioral valence and action plans.

This study investigates the effectiveness of psychological therapies for depression and anxiety symptoms in 7,597 stroke survivors within England’s primary care system. Results show that 71.3% of stroke survivors experienced reliable improvement and significant reductions in symptom scores, underscoring the importance of intervention for improving recovery.

Rhine et al. find that neuronal aging leads to widespread dysregulation of RNA biology, including mislocalization of splicing proteins like TDP-43, chronic cellular stress and reduced resiliency.

Dual cyclin A/B RxL inhibitors selectively kill small cell lung cancer cells and other cancer cells with high E2F activity.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

In active matter systems, increasing density usually reduces activity. Now, in a system where density enhances activity, collective motion is shown to arise from non-motile oscillators when they are confined.

Analysis of blood pressure data from the Million Veteran Program trans-ethnic cohort identifies common and rare variants, and genetically predicted gene expression across multiple tissues associated with systolic, diastolic and pulse pressure in over 775,000 individuals.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Circulating tumor cell (CTC) clusters are much more likely to produce viable metastasis than single CTCs. Here the authors find that the transmembrane protein Plexin-B2 (PLXNB2) mediates homotypic and heterotypic CTC cluster formation, driving lung metastasis in breast cancer mouse models.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Canalized polaritons are light-matter excitations characterized by intrinsic collimation of electromagnetic energy along a specific crystal axis. Here, the authors report the observation of intrinsically canalized phonon polaritons in a single thin layer of a van der Waals crystal, LiV₂O₅.

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.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Low frequency brain waves convey information between regions. Here, the authors demonstrate that for patients with major depression, mood becomes more negative as low frequency waves increase intensity  across the prefrontal cortex.

G_i/o protein-coupled receptors (G_i/o-GPCRs) limit β-cell insulin secretion by decreasing Ca²⁺ entry; however, the underlying mechanism has not been identified. Here, the authors show that G_i/o-GPCRs hyperpolarize mouse and human β-cell membrane potential by activating Na⁺/K⁺ATPases.

The impact of the DART spacecraft on the asteroid Dimorphos is reported and reconstructed, demonstrating that kinetic impactor technology is a viable technique to potentially defend Earth from asteroids.

Designing biodegradable plastics is highly desirable, though it has been a challenge to balance mechanical properties with biodegradability. Here the authors design a multilayered biodegradable composite without compromising the mechanical properties.

Here, the authors report the characterization of stable few-layer PdSe₂ transistors encapsulated in hexagonal boron nitride, showing field effect mobilities up to 700 cm²/Vs at room temperature and signatures of an 8-fold spin-valley degeneracy of the magnetotransport quantum oscillations at cryogenic temperatures.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The choroid plexus (ChP) provides molecular cues for brain development. However, the underlying mechanisms are unclear. This study identifies an apocrine secretion mechanism in the ChP that modulates the CSF protein composition and instructs cortical development.

Chemical doping allows for boosting the conductivity in conjugated polymers but the relationship between doping and the polymers’ complex, multiscale morphology remains elusive. Here the authors report that supramolecular chirality, which up to now had not been considered a parameter relevant to doping, significantly boosts the underpinning redox reaction in conjugated polymer thin films.

Inflammatory monocytes in the brain meninges promote stress-induced fear behaviour, and the pathways involved can be modulated using psychedelic compounds.

The surface topography of breast implants mediates the immune responses to them, and implants with an average roughness of 4 μm largely suppress foreign body response and fibrosis.

Healthy adults were tracked before, during and after high doses of psilocybin and methylphenidate to assess how psychedelics can change human brain networks, and psilocybin was found to massively disrupt functional connectivity in cortex and subcortex with some changes persisting for weeks.

Neurons in the rodent dorsomedial prefrontal cortex encode a flexible internal model of emotion by linking directly experienced and inferred associations with aversive experiences.

This paper characterizes the health impacts in the post-flood year in the United States. The researchers find elevated death risk from floods, primarily due to respiratory diseases, external causes, and specific circulatory diseases.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Here, the authors use passenger mutations to quantify expansion rate in ~6,000 people with mosaic chromosomal alterations in the NHLBI TOPMed cohort, finding associations between growth rate and blood counts along with germline genetic modulators of growth rate.

Inhibition of haem synthesis is shown to lead to the accumulation of branched-chain amino acids in the brown adipose tissue of mice, which reduces UCP1 levels and impairs thermogenesis.