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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.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

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.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

E. coli sequence type 131 is a significant cause of community-onset infection. Here, the authors perform a prospective household-based cohort study in Singapore including samples from humans, companion animals, the environment, and food, to characterise transmission and carriage dynamics.

Biological motors which convert energy into mechanical work inspire the fabrication of synthetic motors. Here the authors demonstrate self-assembled colloidal motors which are driven to a range of responses controlled by the feedback between light polarization and deformation of a liquid crystal.

nELISA miniaturizes the sandwich immunoassay and transforms it into a massively scalable platform for quantitative proteomics.

Light-sheet fluorescence microscopy enables high resolution imaging of biological samples. Here the authors use reflective coverslips to obtain multiple sample views simultaneously, improving the speed of acquisition and resolution compared to dual-view selective plane illumination microscopy.

The authors combine films of two-dimensional semiconductors, which exhibit excitonic spectral features, with SiO₂/Si Fabry-Perot resonators in order to realize topological phase singularities in reflection. Around these singularities, the reflection spectra demonstrate rapid phase changes while the structure behaves as a perfect absorber.

A continuous mesoscale space-time crystal phase is reported from a nematic liquid crystal driven by light.

Dedifferentiated liposarcomas (DDLPS) typically have dedifferentiated (DD) and well-differentiated (WD) components, although their cellular origins remain elusive. Here, the authors characterise primary DDLPS tumours using bulk and single-cell multi-omics and find adipocyte stem cells that could be a common ancestor of WD and DD components.

Here, the authors correlate the position and spectral emission properties of single photon emitters in monolayer WSe₂ with the surrounding local strain potential by combining deep-subwavelength photoluminescence imaging and atomic force microscopy, providing insights on the microscopic mechanisms behind the formation of the quantum emitters.

Single-shot angle-resolved Brillouin light scattering microscopy enables spatiotemporal mapping of mechanical anisotropy in living cells with a spatial resolution below 2 µm and precision in the Brillouin frequency shift of 10 MHz.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Tergaonkar and colleagues identify a noncanonical interaction between the NF-κB transcription factor family member p52 and the ETS family member ETS1. They find that the p52–ETS1 complex is required for splenic germinal center B cell formation and T cell-dependent antibody responses.

Patient-derived xenografts (PDX) could contribute to understanding how colorectal cancer (CRC) responds to targeted therapies like cetuximab. Here, the authors characterise the response to cetuximab in 231 CRC PDXs using multiomics and develop an integrative ensemble classifier - CeSta - to predict sensitivity to cetuximab.

The study of nematic hosts with anisotropic colloidal particles is reported, but not on the chiral counterparts. Here, the authors report on biaxial properties in a system of colloidal rods with designed surface anchoring doped into a chiral nematic host.

A metasurface-based approach is used to implement computationally expensive digital convolution operations in high-speed, low-power optics for improving the latency and power consumption of machine vision systems.

Topological defect structures that swim have been realized in liquid crystals. Now, a range of structures with topology reminiscent of a Möbius strip swim and transform into one another.

Inspired by biology, great progress has been made in creating artificial molecular motors. Here the authors report the synthesis and characterization of the Lawnmower, an autonomous, protein-based artificial molecular motor and show their design is capable of track-guided motion.

The study of neural plasticity has focused on excitatory neural connections, but inhibitory connections can also change. Learning at inhibitory synapses may support high-level cognitive phenomena, such as selecting information for memory storage.

Liquid crystal (LC) applications typically rely on defining the non-topological spatial patterns of the optical axis. Here, the authors demonstrate the topological steering of light by LC nematic vortices, futher establishing an analogy between topological light steering by LC vortices and cosmic strings.

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.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

The communication in active systems plays an important role in their self-organization, yet the detail is not fully understood. Here, Ziepke et al. show the formation of complex structures at multiple scales amongst interactive agents that locally process information transmitted by chemical signals.

X-ray polarimetry observations with the Imaging X-ray Polarimetry Explorer constrain the accretion geometry in an X-ray pulsar and provide evidence for a misalignment of the spin, magnetic and orbital axes in Her X-1.

The formation of soliton macromolecules or metamaterial analogues of polymers with inter-soliton binding resembling strong covalent-like chemical bonds has not been considered so far. Zhao et al. experimentally create and theoretically, model soliton macromolecules, called “polyskyrmionomers”, introducing polymer-mimicking designs of topological chiral meta matter that promise technological utility in data storage and electro-optics.

An atlas study of adipose tissue in people with obesity undergoing weight loss and their lean counterparts reveals that weight loss reduces cell senescence but cannot reverse all the metabolic problems caused by obesity.

Researchers demonstrate systems in which optical solitons coexist and interact with topological solitonic structures localized in the molecular alignment field of a soft birefringent medium. The findings could lead to solitonic tractor beams and new light–matter self-patterning phenomena.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Muography takes advantage of the high penetrating power and relativistic nature of cosmic-ray muons for imagery; positioning, navigation, timing; and secured communications. This Primer provides an overview of muography techniques, describing how they are used in Earth and planetary sciences, computer science and social science.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Soft magnetic materials are critical components of electric motors, generators and transformers, however obtaining a material that is magnetically soft, but mechanically robust and stable at high temperature is very difficult. Here, Han et al succeed in combining these disparate properties by introducing ferromagnetic Widmanstätten patterned intermetallic precipitates into a ferromagnetic alloy matrix.

Unstructured light controls the elastic monopole moments of nematic liquid-crystal colloidal particles and switches them to quadrupoles, with like-charged monopoles attracting and oppositely charged ones repelling, enabling reconfigurable dynamic self-assembly.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Insulating molecular layers on the basal plane of 2D perovskite is a major bottleneck for charge injection that limiting device performance. Here, the authors show that plane-contacted graphene functions as a low barrier and gate-tunable contact to overcome this limitation.

Molecular diagnostics for tuberculosis have focused on predicting drug susceptibilities in a binary manner (i.e., strains are either susceptible or resistant). Here, CRyPTIC Consortium researchers use whole genome sequencing and a quantitative assay to identify associations between genomic mutations and minimum inhibitory concentrations in over 15,000 Mycobacterium tuberculosis clinical isolates.

Bhattacharjee and Schaeffer et al. map exclusive breastfeeding (EBF) in 94 low- and middle-income countries (LMICs), finding increased EBF practice and reduced subnational variation across the majority of LMICs from 2000 to 2018. However, only six LMICs will meet WHO’s target of ≥70% EBF by 2030 nationally, and only three will achieve this in all districts.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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.