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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.

When doubly-degenerate band crossings known as Kramers nodal lines intersect the Fermi level, they form exotic three-dimensional Fermi surfaces composed of massless Dirac fermions. Here, the authors present evidence that the 3R polytypes of TaS₂ and NbS₂ are Kramers nodal line metals with open octdong and spindle-torus Fermi surfaces, respectively.

The authors report superconducting topological surface states (TSS) on MBE-grown Fe(Te,Se) films by high-resolution laser-ARPES. Near the FeTe limit, the surface state disappears due to an electron-correlation-driven topological transition associated with decoherence of the d_xy-orbital-derived bands.

Marine worms possess camera-type eyes. Here they show that the growth of marine annelid eyes depends on a stem cell system reminiscent of vertebrate eyes. Moreover, eye development seems to be tuned by a light-sensitive opsin known from vertebrate vision.

Across 13 longitudinal studies (3,737 adults), the authors show that brain atrophy parallels memory loss, with a stronger coupling in later life. APOE ε4 increases decline, yet genetic risk does not modify the brain–memory relationship.

Using a zebrafish-based screen, Civiletto and colleagues identify the herb-derived metabolites thymol and carvacrol as activators of autophagy and mitophagy, demonstrating their therapeutic potential in C. elegans and mouse models.

As presented at the ESMO Congress 2025, in the single-arm phase 2 IKF/AIO PHERFLOT trial, the perioperative combination of FLOT chemotherapy with anti-PD-1 and anti-HER2 monoclonal antibodies led to a pathological complete response rate of 48.4% in patients with resectable HER2+ esophagogastric adenocarcinoma, meeting the prespecified co-primary endpoint.

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.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Natural physical and biological systems change in regions of temperature increase. Such changes have occurred on all continents and in most oceans since at least 1970. This paper presents statistical evidence that these changes cannot be explained by natural climate variations alone, and concludes that anthropogenic climate change is affecting physical and biological systems globally and on some continents.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

The combination of fast photo-response and high gain plays a pivotal role in photodetector devices. Here the authors combine a colloidal quantum dot photodiode with a graphene phototransistor to overcome the speed, quantum efficiency and linear dynamic range limitations of available phototransistors.

Active control of optical fields at the nanoscale is difficult to achieve. Here, the authors fabricate an on-chip graphene NEMS suspended a few tens of nanometres above nitrogen vacancy centres and demonstrate electromechanical control of the photons emitted by electrostatic tuning of the graphene NEMS position.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

A spatial taxonomic framework integrating genomic, morphological, ecological, life history and acoustic data is used to clarify the cryptic evolution of the taxonomically controversial mouse lemur complex, with a view to aiding future conservation of this and other similarly cryptic clades.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Mixed ionic–electronic transport in conducting polymers remains poorly understood. Here the authors observe non-equilibrium electronic transport when counterions are unable to equilibrate in response to gate-injected electronic carriers.

Images collected during NASA’s DART mission of the asteroid Didymos and its moon, Dimorphos, are used to explore the origin and evolution of the binary system. Authors analysis indicate that both asteroids are weak rubble piles and that Didymos’ surface should be about 40 to 130 times older than Dimorphos.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Molecular simulations reveal how diamond and graphite crystallize from molten carbon. Following Ostwald’s step rule, the liquid’s low density drives metastable graphite formation even within the diamond thermodynamic stability zone, explaining discrepancies in high-pressure carbon phase experiments.

Analysis of a large ancient genome dataset shows that genetic risk for multiple sclerosis rose in steppe pastoralists, providing insight into how genetic ancestry from the Neolithic and Bronze Age has shaped modern immune responses.

The authors report on a determination of the momentum transferred to an asteroid by kinetic impact, showing that the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

A collaborative study initiated by the sovereign nation of Picuris Pueblo in the Northern Rio Grande region of New Mexico addresses gaps in traditional knowledge and furthers understanding of their population history and ancestry.

Van der Waals antiferromagnets offer a unique platform for studying magnetism in reduced dimensions, however, the low dimensionality, combined with lack of net magnetization, renders investigation challenging with conventional experimental probes. Here, Houmes et al show how van der Waals antiferromagnets can be investigated via the resonances of a vibrating rectangular membranes of this material.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

Double Asteroid Redirection Test (DART) mission impact on asteroid Dimophos resulted in an elliptical ejecta plume. Here, the authors show that this elliptical ejecta is due to the curvature of the asteroid and makes kinetic momentum transfer less efficient.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

This cross-sectional study in two independent middle-aged and aged cohorts investigates whether psychological characteristics associated with varying dementia risk aggregate into psychological profiles and relate to aging brain health.

Wastewater is a promising source of data for continuous monitoring of pathogens in communities, but analysis protocols and methods are still being established. Here, the authors develop sequencing and analysis protocols and use them to evaluate the microbial content of longitudinal wastewater samples from Miami-Dade County, USA.

FLuID enables privacy-preserving knowledge sharing in drug discovery using knowledge distillation. The results show that the approach expands applicability domains and fosters collaboration across organizations without compromising data privacy or security.

Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Spatially resolved images of M87 obtained at a wavelength of 3.5 mm in 2018 show a ring-like accretion structure, the inner (outer) edge of which connects the black hole (jet).

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.

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

A study of two childhood cases of herpes simplex encephalitis shows that TMEFF1 interacts with the HSV-1 cell-surface receptor NECTIN-1, preventing HSV-1 from fusing with the cell membrane and entering cortical neurons.

An online approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups has been developed to help to improve current diagnostic standards.

As presented at the 2025 ASCO Annual Meeting, intracerebroventricular infusion of bivalent CAR T cells targeting EGFR and IL-13Rα2 in patients with multifocal, recurrent glioblastoma was feasible and well tolerated, with the maximum tolerated dose identified, one patient with a partial response and one patient with durable stable disease.

Emerging weather patterns over recent decades are exacerbating extreme precipitation and heatwaves in the tropical Indo-Pacific region, according to a computation of trends in reanalysis data.