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People living with multiple long-term conditions often experience reduced quality of life, but evidence from Southeast Asia is fragmented. Here the authors show that commonly used tools indicate moderately reduced yet generally good quality of life, highlighting the need for context-sensitive measurement approaches.

For Nature Aging’s fifth anniversary, we acknowledge the essential work that is done by our colleagues, without which Nature Aging’s monthly publication would not be possible. We speak with some of our internal colleagues about the process of making a journal every month. Rebecca Roberts is a production editor at Springer Nature, Mark McGranaghan is a senior sub editor, Lauren Snape is an art editor and Amanda Karmolinski is a senior editorial assistant. In this Q&A, Rebecca, Mark, Lauren and Amanda pull back the curtain and tell us about the various roles that go into putting it all together.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

In this work, the authors reveal that three non-ribosomal peptides targeting a common protein quality system differentially alter the Mycobacterium tuberculosis proteome, providing new insight into the molecular mechanisms behind their antimycobacterial activity.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Deep brain stimulation tuned to cue-reactivity within the nucleus accumbens region reduced drug cravings, heralding an evocation-based programming strategy for opioid use disorder.

This paper reports the excess mortality estimated during the evolving consecutive waves of COVID-19 in countries participating in the European Mortality Monitoring Network (EuroMOMO) in 2020-2023 and how they compare to recent influenza seasons.

Doxycycline has been recommended as post-exposure prophylaxis for prevention of bacterial sexually-transmitted diseases. Here, the authors use mathematical modelling to investigate the potential disease, antimicrobial resistance, and economic implications of this intervention in gay, bisexual, and other men who have sex with men in Australia.

TREM2 is an important AD risk factor playing essential roles in the microglial response to amyloid pathology. Here, authors show using a TREM2 reporter mouse that TREM2 levels are critical for efficacy of TREM2 agonism informing current clinical efforts.

This study shows that CrSBr hosts Frenkel-like and Wannier-Mott-like excitons whose distinct spatial character explains their contrasting sensitivity to magnetic order and lattice vibrations, challenging the standard dichotomy in describing excitons.

This work demonstrates the first miniature RF filter combining ultrawide tunability (4–18 GHz) and high nonreciprocity, achieving low loss, zero static power, and compact size (1 cc).

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

Here the authors present NCATS-SM0225, a small molecule that inhibits ERAD and selectively kills cancer cells by binding VDACs, disrupting calcium homeostasis, and triggering the PERK-STIM1 pathway to degrade ERAD regulators.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Lucerastat was well-tolerated, but did not reduce neuropathic pain, abdominal pain, or diarrhea compared with placebo. Lucerastat reduced biomarkers of Fabry Disease at 6 months, and these reductions were maintained at the 18-month interim analysis.

Cosgun et al. show that, in B cell leukemia, β-catenin expression is maintained at low levels through glycogen synthase kinase 3B (GSK3β)-mediated phosphorylation. Inhibition of GSK3β results in β-catenin–Ikaros–NuRD complex formation, leading to B-ALL cell death through MYC repression.

The properties of electronic transport through edge states of three-dimensional quantum Hall-like states are not yet resolved. Now, increasing the surface area of the edges is shown to produce increased conductance, suggesting that chiral surface states are present.

Calcium imaging of mouse hippocampal neurons while mice learn a reward-based task over several weeks provides insight into the evolution of the hippocampal reward representation during extended periods of experience.

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.

Climate limits where insects can live and which species can coexist. Using thermal tolerances of 653 moths on Asian mountains, this study shows warmer temperatures broaden thermal tolerance traits diversity; daily variation has little influence, and strong seasonality mildly weakens this pattern.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

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.

Accurate determination of population size for highly-mobile marine animals is often prohibitively difficult. Here, Bravingtonet al.estimate the abundance of southern bluefin tuna using a method based on the number of parent-offspring pairs detected genetically in samples from the catch.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

This study addresses opioid misuse prediction by integrating physiological data and electronic health records. Utilizing personalized deep-learning models, it achieves a high accuracy in risk assessment through entropy feature extraction and relevance-based temporal fusion, demonstrating effective intervention potential.

The reconstructed Holocene Australian summer monsoon in this study, together with the Asian monsoon records, show that the coupling evolution of Holocene Asian-Australian monsoon was dominated by the thermal imbalance between two hemispheres.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Experimental evidence demonstrates long-distance remote epitaxial interactions of thin films even through thick amorphous carbon buffer layers and shows that these can be induced through dislocations in the substrate.

This study advances methods for benchmarking macromolecular complex predictions by introducing a scalable open-source framework used in recent community assessments to compare structures, interfaces and ligand interactions against experimental data.

NiPS₃ is a van der Waals antiferromagnetic semiconductor where the exciton formation is strongly influenced by the magnetic ordering. Previous studies have been limited to magneto-optical approaches, but here, Lebedev, Gish and coauthors succeed in making field effect transistors that operate below the Néel temperature and observe an ultranarrow electroluminescence with a high degree of linear polarization.

Wearable devices generate vast streams of health data, but making sense of these measurements requires complex numerical reasoning beyond the reach of conventional language models. This study introduces a large language model agent that interprets wearable data to deliver accurate, personalized health insights.

A national classification system of wetland hydrologic connectivity to streams, which could be applied globally, demonstrates and advances current understanding of how wetland connectivity affects surface water quality.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

Provencio and colleagues reported the exploratory efficacy outcomes and safety results from the CheckMate 77T phase 3 trial in patients with stage III resectable non-small-cell lung cancer.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Termites, the largest lineage of non-hymenopteran social insects, are important decomposers of plant organic matter in the tropics. Here, the authors sequence the genomes of 45 termites and two cockroach outgroups and investigate the influence of diet on the evolution of termite genomes.

The authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.

During the Last Glacial Maximum, the deep Northwest Atlantic was only about 2 °C colder than today, suggesting sustained production of relatively warm North Atlantic Deep Water during the Last Glacial Maximum.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

Natural genetic variation of photosynthesis is an underexplored resource for plant genetic improvement. Here, the authors find allelic variations of YS1 affect Arabidopsis photosynthesis acclimation using genome-wide association study, reverse genetics, and quantitative complementation approaches.

SpbK protects Bacillus subtilis from phage infection by depleting NAD⁺. In this study, the authors uncover the molecular mechanisms underlying SpbK’s self association-dependent NADase activity and its activation by the SPβ phage portal protein YonE.

Man-made ammonia emissions have harmful effects on human health and ecosystems, yet global mitigation strategies remain underexploited. A study now finds that emissions could be halved cost-effectively by 2050 through targeted and prioritized measures, with benefits far outweighing costs.

Arterial development is critical for proper blood flow, but the mechanisms mediating this process at the organ level remain unclear. Here, they show that a subpopulation of endothelial cells is important for formation of arterial endothelium in the intestine.