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The authors introduce a new approach to microwave impedance microscopy, eliminating once-indispensable specialized probes and cancellation circuits. Using monolithic silicon probes and a streamlined architecture, they achieve 0.26 zF/√Hz sensitivity and 15 nm resolution with drift-free operation.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Here, authors demonstrate an ultrafast time-gating protocol using a sub-micron-thick layer of epsilon-near-zero indium-tin oxide, yielding a strong four-wave mixing signal while reducing scattering and scintillation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening severe cutaneous drug reaction mediated by CD8⁺ T cells. Here the authors characterise the immune response in skin samples at the site of tissue damage from patients affected with SJS/TEN and compare this to healthy skin or blister fluid and find populations of CD8⁺ T cell clonotypes expressing cytotoxic mediator molecules.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

The end of 2015 saw the passing of John F. Kurtzke and Richard T. Johnson, two legends in neurology, and founding fathers of neuroepidemiology, neurovirology and neuroimmunology. Here, we pay tribute to these two giants by discussing their impact on the genesis of these profoundly important disciplines.

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

Plasma p-tau217 tests used to develop clocks that predict when cognitively unimpaired individuals would develop symptoms of Alzheimerʼs disease.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

While therapies targeting type I BRAF mutations have been developed, there are limited options for those with type II and III mutations. Here, the authors identify a subset of BRAF-mutant non-small cell lung cancer patients and characterise the pan-RAF inhibitor exarafenib, demonstrating efficacy in preclinical models and investigating subsequent resistance mechanisms.

The role of individual lipid species in Alzheimer’s disease (AD) is not fully understood. Here, the authors performed global lipidomics on post-mortem dorsolateral prefrontal cortex collected from 316 participants in the ROSMAP cohort including asymptomatic and symptomatic AD.

To accelerate therapeutic development and equip stakeholders with clear benchmarks, the authors outline target product profiles for therapies designed to delay or prevent the onset of clinical symptoms of Alzheimer’s disease.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Understanding why people hesitated to seek COVID-19 vaccines after they became available can inform public health policies. Here, the authors use search engine data to infer vaccination rates and intentions across the United States, then develop a taxonomy of vaccine concerns and identify the most prevalent apprehensions.

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.

Solid contacts on a microscopic level are widely described by a classical contact mechanics theory. Here Styleet al.show that this theory breaks down when a small particle adheres to a soft surface where a fluid-like behaviour is observed because of the predominant role played by surface tension.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

An implantable vagus nerve-targeted device safely reduces disease activity and joint damage in rheumatoid arthritis, offering a new nondrug treatment for patients who do not respond to or cannot tolerate medication.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

There is a need for an easy-to-use clinical tool, that could predict favorable early PSA response and subsequently enhance early risk stratification, as well as guide treatment planning. Here, the authors show that based on patient data from four phase III randomized trials, Nadir androgen receptor pathway inhibitor (APRI)- Derived Integrative Response (NADIR) model predicts favorable early PSA response to ≤0.2 ng/mL by 6 months in metastatic hormone sensitive prostate cancer (mHSPC) patients initiating treatment with an APRI.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Early-life exposure to allergens triggers a distinct local mode of dendritic cell activation in neonatal skin without requiring migration to lymph nodes, which shapes responses to allergens in later life.

Intelectin-2 defends mucosal interfaces by crosslinking mucus and blocking microbial growth. This study reveals that mouse and human intelectin-2 recognizes galactose-rich glycans to bind and target diverse bacteria—uncovering a potent, dual-action lectin that shapes host–microbe balance.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The cytochrome bc₁ oxidase of Mycobacterium tuberculosis is a potential target in the fight against tuberculosis. Here, the authors evaluate the potential of cytochrome bc₁ inhibitors as partner drugs in tuberculosis treatment regimens.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

Kinases regulate cellular processes, making their study essential for understanding cellular function and disease. Here, the authors evaluate methods to infer kinase activity from phosphoproteomics data and provide a toolkit to evaluate future methods.

Gold samples can be heated to more than 14 times their melting point while retaining their crystalline structure, far surpassing the predicted entropy catastrophe threshold and suggesting a substantially higher or potentially no limit for superheating.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

It has been suggested that operating sensors far from thermodynamical equilibrium can enhance signal-to-noise ratio in a way which breaks the standard limits coming from stochastic fluctuations. Here, the authors show how this can in principle allow an arbitrarily large signal-to-noise ratio.

Due to a paucity of terrestrial data, knowledge of the size of the East Antarctic ice sheet in the past is limited. Here, the authors present isotope data of sulfates from the Lewis Cliff Ice Tongue moraine, which suggest temporary existence of ice-free conditions in central Antarctica since the Miocene.