Search

This paper uses multiomics to profile a large cohort of meningioma samples to highlight the role of the tumor microenvironment in driving the epigenetic changes underpinning tumor classification and prediction of outcome.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

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

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.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

A meta-analysis of 168 studies reveals that economic inequality is not significantly associated with subjective well-being or mental health.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

Previous malaria exposure weakens whole-parasite malaria vaccines by leaving haemozoin, which impairs T cell activation. An mRNA vaccine bypasses this block, restores protective T cells and improves protection when combined with whole-sporozoite vaccination.

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.

The variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

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.

Smith et al. present M-PACT, a deep neural network leveraging low-input cell-free DNA methylation profiles to achieve robust classification of pediatric brain tumors and enable cellular deconvolution and sensitive copy-number variation detection.

The microbial metabolite trimethylamine (TMA), the precursor of TMAO, which is associated with adverse cardiometabolic outcomes, is shown to have beneficial metabolic and anti-inflammatory effects in the host in the context of obesity.

In a randomized controlled trial that included 97 participants, 69% patients with Crohn’s disease (CD) allocated to a fasting-mimicking diet (FMD) achieved clinical response, and over 60% reached remission, outperforming the control group. The FMD also reduced markers of intestinal inflammation, suggesting this dietary intervention could serve as adjunctive treatment for CD.

Murphy et al. reveal a unifying pathogenetic mechanism according to which diverse mutations in the muscle-specific ribosomal protein RPL3L cause severe neonatal dilated cardiomyopathy, establishing a framework for interpreting the growing spectrum of RPL3L variants.

This Article details the methods used for rigorous assessment of disease interventions in a multicenter preclinical trial. Using stroke models as proof of concept, it offers adaptable protocols for any field requiring robust preclinical validation.

Hall resistance quantization measurements in the quantum anomalous Hall effect regime on a device based on the magnetic topological insulator V-doped (Bi,Sb)₂Te₃ show that the system can provide a zero external magnetic field quantum standard of resistance.

Pathogenic variants in KIF1A give rise to KIF1A-associated neurodegenerative disorder (KAND). Here, the authors use antisense oligonucleotides targeting common polymorphisms to knock down pathogenic KIF1A expression in patient-derived stem cells.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Analysis of the longest-lived mammal, the bowhead whale, reveals an improved ability to repair DNA breaks, mediated by high levels of cold-inducible RNA-binding protein.   

Widespread ecosystem degradation demands scalable strategies for plant establishment — the process of successful seed dispersal and burial that enables a seed to germinate, survive its vulnerable early stages and emerge as a resilient seedling. However, harsh environmental conditions often make conventional seeding efforts costly and ineffective. Inspired by natural seeding mechanisms that exploit environmental cues, emerging biodegradable, stimulus-driven morphing matter-enabled machines can support plant establishment across its critical phases, offering a pathway to low-impact ecological restoration.

Data obtained from the MicroBooNE liquid-argon time projection chamber are used to exclude the single light sterile neutrino interpretation of the LSND and MiniBooNE anomalies at the 95% confidence level.

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.

Magnetic reconnection, thought to drive solar eruptions, has been studied with remote sensing. The Parker Solar Probe has directly measured reconnection-associated plasma properties in situ in the solar corona, deepening our understanding of the process.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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.

The cellular differentiation states of paediatric rhabdomyosarcoma (RMS) remain to be explored. Here, single-cell RNA sequencing analysis of RMS tumours reveals an immunosuppressive microenvironment and distinct transcriptional programs predictive of patient outcomes.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

LEVA is a label-free immobilization method for studying surface-bound extracellular vesicles.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Here the authors reveal how replication stress in BRCA2-deficient cells triggers a mutagenic cycle of APOBEC3B upregulation, uracil accumulation at stalled forks, and DNA damage, uncovering a self-reinforcing loop that fuels genomic instability.

The location of EGFR exon 20 loop insertions (EGFRex20ins) has been shown to alter sensitivity to lung cancer therapy. Here, the authors report the results of the ZENITH20 clinical trial investigating poziotinib (EGFR TKI) in lung cancer patients and, combining with a similar trial, investigate how structural differences due to location of EGGFRex20ins alters sensitivity to EGFR TKI.

In clinical and population-based cohorts, a strong contribution of polygenic risk for type 2 diabetes (T2D) significantly modifies the onset and phenotypic variability of maturity-onset diabetes of the young (MODY). This polygenic T2D burden may also account for MODY-like individuals without identified monogenic causes.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Singla et al. report the secondary analysis of the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) trial.