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Nitrogen-centered radicals are valuable intermediates for the controllable and selective functionalization of remote inert C(sp³)–H bonds. Here, the authors report an amidyl radical-triggered, metal-free and site-selective C(sp³)–H heteroarylation of amides under photoredox conditions.

Intermolecular cyclization reactions using nitrogen-containing building blocks are scarce. Now, bifunctional sulfilimines have been shown to enable the modular construction of a diverse range of N-heterocycles by reacting with alkenes in a single photocatalysed step. Both sulfilimines and alkenes are easily accessible, providing access to a wide range of N-heterocycles with different ring types, ring sizes and substituents on the skeleton.

Single-photon optical nonlinearity is possible using an optical cavity to create strong coupling between a cavity mode and a two-level quantum system. Here, the authors demonstrate it is also possible in the weak-coupling regime by using quantum interference in a polarization-degenerate cavity.

Landau states are associated with the quantised orbits of charged particles in magnetic fields. By manipulating electron vortex beams in a magnetic field, this study reconstructs the internal quantum dynamics of free-electron Landau states, which differs strongly from the classical cyclotron rotation.

Aluminium alloys can naturally age and form microstructural clusters that affect their mechanical properties. Here, the authors show that nanosized samples do not under undergo natural aging because diffusion-controlled clustering processes are inhibited.

Cultivation of tropical soil microorganisms combined with physiological experiments and bioinformatics analyses identify a family of clade III lactonase-type nitrous oxide reductases with low sequence identity but high 3D structural similarity to known nitrous oxide reductases.

Lösel, Relle et al. present a biomechanical approach and visualisation tool for incisional hernia repair using two CT scans, one at rest and one during a Valsalva manoeuvre, to assess abdominal wall instability and guide surgical planning. In 31 patients treated with this method, all remained pain-free and had no hernia recurrence after three years.

Olfactory perception shows marked sexual dimorphism, yet its genetic basis remains underexplored. Here, the authors show sex-specific and shared genetic loci for odour identification, implicating olfactory receptor clusters and links to Alzheimer’s disease risk.

The identification of molecular biomarkers in cancer of unknown primary site (CUP) cases may enable the improvement of prognosis in these patients. Here, the authors integrate whole genome/exome, transcriptome and methylome data in 70 CUP patients, recommend therapies based on their analysis and report clinical outcome data.

A longitudinal multiomics analysis of a patient with multiple myeloma who developed peripheral T cell lymphoma after treatment with anti-BCMA CAR T cells and a GPRC5D-directed bispecific antibody reveals that two mutated CAR⁺CD8⁺ T cell clones were probably drivers of the neoplasm.

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.

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.

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.

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

Bull et al. developed a mathematical model for how bacteria colonise urinary catheters. The model reveals that different strategies may be needed to reduce catheter associated infection for long-term vs short-term catherised patients

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Here, Heitmann et al. report results from a Phase I/II trial evaluating CoVac-1, a peptide-based T-cell activator, in patients with B-cell deficiency, demonstrating potent induction of SARS-CoV-2-specific T-cell responses along with a favorable safety profile.

Artificial-intelligence algorithms could identify scientists who need support with translating their work into real-world applications and more. Leaders must step up.

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

Microbial reduction of nitrous oxide to dinitrogen is considered negligible under acidic conditions. However, Guang He et al. show that a co-culture of two bacterial species derived from acidic tropical forest soil can reduce nitrous oxide at pH 4.5.

Magnetic resonance imaging of swollen tendons suggests that the elasticity and stress relaxation of extracellular matrix depend on electrostatic repulsions between proteoglycans rather than on hydration-associated changes.

Standard of care for unfavorable-risk cancer of unknown primary (CUP) comprises platinum-based chemotherapy as first-line treatment, however therapeutic options remain limited. Here the authors report the results of a phase II trial of combined nivolumab (anti-PD1) and ipilimumab (anti-CTLA4) in patients with unfavorable CUP.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Advances in electron microscopy are enabling ever smaller features to be probed, with the measurement of atomic electric fields standing as a major challenge. Towards that aim, Müller et al.present a simplified theoretical approach for enhancing the resolution in differential phase contrast microscopy.

Researchers seeking the latest biotechnology expertise have several options. Paul Smaglik reports.

Mechanisms of distinct resonance in microcavities driven by strongly detuned single quantum dots are not well understood. Investigation of non-resonant dot–cavity coupling of individual quantum dots in micropillars now suggests a dominant role of phonon-mediated dephasing. This new perspective may have implications for single-photon sources, quantum information applications and spectroscopy.

The observation of so-called Bogoliubov excitations provides the first sign of possible superfluid behaviour in an exciton-polariton condensate.

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