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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.

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.

Polysulfur compounds have been ascribed as the unknown near-UV absorbers in Venusian atmosphere and play a key role in the sulfur chemical cycle of this planet. Here, authors establish their production from (SO)₂ on the grounds of quantifications of photochemical and thermal pathways involved in the sulfur chemical cycle of the planet.

In a double-blind, placebo-controlled phase 2 trial in patients with metastatic renal cell carcinoma treated with anti-PD-1 plus a VEGFR tyrosine kinase inhibitor, donor fecal microbial transplantation (FMT) from complete responders to immunotherapy did not significantly improve the primary endpoint of 12-month progression-free survival (PFS) but did significantly improve median PFS versus placebo FMT.

This study examines long-term changes in species richness across tropical forests in the Andes and Amazon. Hotter, drier and more seasonal forests in the eastern and southern Amazon are losing species, while Northern Andean forests are accumulating species, acting as a refuge for climate-displaced species.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

The cis-regulatory elements encoded in the sequence and structure of mRNAs determine their translational output. Here the authors develop NaP-TRAP, an assay to measure translation in a frame-specific manner, revealing dynamic regulatory elements in zebrafish embryos and HEK293T cells.

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.

Voltage‐gated potassium channels allow nerve communication by coupling voltage sensing to pore opening. Here, the authors applied rapid temperature steps and mutations to map the channel’s energy landscape, revealing how distinct energy barriers contribute to channel activation.

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.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Wood density is a key control on tree biomass, and understanding its spatial variation improves estimates of forest carbon stock. Sullivan et al. measure >900 forest plots to quantify wood density and produce high resolution maps of its variation across South American tropical forests.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

An analysis of viral genomes and epidemiological data from the 2022 mpox outbreak in Portugal sheds light on the heterogeneity of early transmission events, with national and international linkages.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

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.

The monoclonal antibody S309, identified from memory B cells of an individual infected with SARS-CoV in 2003, or antibody cocktails that contain this antibody potently neutralize SARS-CoV-2.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

Single-cell DNA methylome profiling allows the study of epigenomic heterogeneity in tissues but has been impeded by library quality. Here the authors demonstrate snmC-seq2 which improves mapping, throughput and library complexity.

Lanzavecchia and colleagues use single-cell B cell receptor sequencing to examine the clonal structure, stability and dynamics of the B cell repertoire and the relationship between memory B cells and newly generated plasma cells in humans.

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Polygenic scores derived from genome-wide association analyses of hypertrophic cardiomyopathy and genetically correlated left ventricular traits effectively stratify risk of disease and adverse outcomes in the general population and across clinical cohorts.

91% of Brazil’s garimpo activity is in the Amazon, where almost 40% of them are five years old or younger. This paper finds in 2022, 77% of the detected garimpos showed explicit signs of illegality.

Here, the authors show that the time elapsed between Zika infection and subsequent dengue virus infection affects the magnitude and durability of the antibody and cell-mediated immune responses against dengue virus, but not viremia. This research in non-human primates has implications for co-endemic regions and vaccination.

The electrocardiogram (ECG) is the most commonly used exam for the screening and evaluation of cardiovascular diseases. Here, the authors propose that the age predicted by artificial intelligence from the raw ECG tracing can be a measure of cardiovascular health and provide prognostic information.

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.

Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

Khader and colleagues show Mycobacterium tuberculosis (Mtb)-specific B cells are needed to recruit T_FH cells into follicular-like structures within lung granulomas to control the Mtb bacilli; however, specific antibodies and many conventional properties of B cells are dispensable.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

The authors report genome-wide data from 34 ancient individuals spanning the Holocene, from what is now Brazil, illuminating connections and disjoints between Sambaqui shellmound societies and preceding and later peoples.

Convergent mutations in hot spots of the spike proteins of currently circulating SARS-CoV-2 Omicron variants increase the binding affinity for the host receptor and promote more efficient fusion with host cell membranes.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.

Cryo-electron microscopy structures of the thyrotropin receptor reveal the basis for the activation of the receptor by autoantibodies in patients with Graves’ disease.

The desmoplastic stroma constitutes part of the microenvironment in pancreatic ductal adenocarcinoma. Here the authors show that Class I HDACs regulate the pro-desmoplastic and pro-tumorigenic transcriptional programs to support stromal activation and tumour progression.

Antibodies against dengue virus (DENV) can increase Zika virus (ZIKV) infectionin vitro, but their role in vivoremains largely unknown. Here, the authors show that pre-existing immunity from a 2.8 years earlier DENV infection does not affect ZIKV pathogenesis in macaques but instead shortens Zika viremia.

Inflammation promotes insulin resistance in adipocytes, but the mechanism is unclear. Here, the authors show that the inflammatory transcription factor IRF3 drives expression of AIG1, which encodes a hydrolase that breaks down a class of insulin-sensitizing lipid called FAHFAs.

Pseudovirus assays and surface plasmon resonance show that the Omicron receptor-binding domain binds to human ACE2 with increased affinity relative to the ancestral virus, and that most neutralizing antibodies are considerably less potent against Omicron.

In xenograft tumour models in mice, modulation of dietary serine, serine palmitoyltransferase or phosphoglycerate dehydrogenase activity enables control of the endogenous synthesis of deoxysphingolipids, sensitizing the tumours to metabolic stress and slowing their progression.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.