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Newly emerging SARS-CoV-2 variants underscore the need for broad-spectrum antiviral solutions. This study shows a macrocyclic peptide inhibitor that locks the SARS-CoV-2 spike trimer into a “closed” conformation by engaging a conserved region, and demonstrates that intranasal administration of the peptide inhibitor protects against Omicron variants.

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.

Metastatic triple negative breast cancer (mTNBC) has limited treatments options. Here, this group presents a combination of low-dose cyclophosphamide, anti-CSF1R, and anti-PD-1 therapies to boost immune cell infiltration and reduce recurrence in aggressive TNBC models.

Cryo-electron microscopy structures of three large ornate natural bacterial RNA molecules reveal their quaternary structures and intra- and intermolecular interactions that stabilize them.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

MATTERIX, a multiscale graphics processing unit-accelerated framework for high-fidelity digital twins and workflows of chemistry laboratories, is presented, simulating robot and device operation, fluids and powders, and processes such as heat transfer and chemical kinetics.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

The authors show that electronic thermal transport in an in-plane magnetic field in compressively strained HgTe at the Weyl points follows the Wiedemann–Franz law, challenging predictions of gravitational-anomaly signatures in this system.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

A high-resolution transcriptomic and epigenomic cell-type atlas of the developing mouse visual cortex from embryonic to postnatal development is presented, providing a real-time dynamic molecular map associated with individual cell types and specific developmental events.

Using extended-gate capacitive coupling and diode connection, stretchable biosensors with a built-in differential circuit design can be created that can offer low signal distortion under bias stress instability, uniaxial strain, compression and temperature variations.

Here, the authors investigate chromatin-based gene regulation in the closest relative of animal, choanoflagellates. They uncover a putative dual role for the histone modification H3K27me3 in regulating of protein-coding genes during differentiation and transposable elements.

Cellular state cooccurrence signatures, such as carcinoma ecotypes may serve as potential biomarkers of response to cancer immunotherapy, however, their clinical utility remains unexplored. Here, the authors analyse large real world immunotherapy cohorts and gene expression data and develop a predictive model for response.

A novel covalent inhibitor, ISM3312, targets the main protease of multiple human coronaviruses, including drug-resistant strains, and shows broad antiviral activity. It offers a promising therapeutic strategy against current and future coronavirus threats.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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.

Helicity of photons is exploited for preferential emission direction and sorting of valley-polarized excitons is achieved at room temperature.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Preliminary results from a phase 2a trial involving 71 patients suggest that a new agent, discovered and designed with artificial intelligence assistance, is safe and effective for the treatment of idiopathic pulmonary fibrosis.

High-density multimodal soft bioelectronic fibres provide a platform for minimally invasive implantable electronics, where diverse sensing and stimulation functionalities can be effectively integrated.

Recent studies integrating multi-omics data with cell atlases across development for brains of humans and model organisms are revealing conserved and divergent patterns of brain development at the molecular and cellular levels, and linking these to complex behavioural and neuropsychiatric phenotypes.

A hidden effect can occur in materials where locally a symmetry is broken, even though global symmetry is preserved. An example is hidden spin-polarization, arising from local inversion symmetry breaking in otherwise globally centro-symmetric materials. Here, Yuan et al uncover a hidden spin-polarization that can occur in antiferromagnets without spin-orbit coupling and identify the key material requirements for this to occur.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

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.

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.

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.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

Tracking raw materials is critical for securing global supply chains, but traditional tags lack in traceability and anticounterfeiting. The authors present a DNATag-based system for secure traceability, featuring error tolerance, mobile phone readability, and robust forgery protection.

The impact of perioperative organ injury on surgical outcome is not well understood. Here the authors show the overall impact and the impact of individual perioperative organ injuries in 28 million surgical patients in Germany.

How signaling pathways recruit SWI/SNF chromatin remodeling complexes is not known. Here the authors suggest a ubiquitin directed mechanism targeting SWI/SNF for Wnt pathway dependent transcription, important for development and cancer.