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Comprehensive benchmarking of computational methods for the prognostic significance of tumour-infiltrating lymphocytes (TILs) in breast cancer remains elusive. Here, the authors perform multi-centric validation and evaluation of multiple cTILs methods in a large cohort of triple negative and HER2+ breast cancer patients.

DGAT1 controls sex-specific CD8⁺ T cell responses in tumours, reducing mitochondrial function and tumour control in female mice, but protecting against oxidative stress and tumour growth in male mice through androgen receptor signalling.

The emissions of leading fossil-fuel and cement producers have been systematically linked to particular heatwaves. Three scientists discuss the methodology behind the result and its potential impact on climate-liability court cases.

Early detection of coronary artery disease is crucial to mitigate cardiac complications. Here, the authors show how machine learning can enhance risk stratification, and potentially reduce unwarranted invasive testing by integrating widely accessible clinical data and stress test ECG signals.

A hallmark feature of the high-temperature superconducting cuprates is the so-called pseudogap regime, an exotic state of matter, displaying Fermi arcs and a momentum-selective suppression of spectral weight upon cooling. Here, the authors investigate the pseudogap in the Emery model and set our results in perspective to a wide variety of experiments.

A machine-learning algorithm based on an array of demographic, physiological and clinical information is able to predict, hours in advance, circulatory failure of patients in the intensive-care unit.

In angle-resolved photoemission spectra, nearly vertical energy-momentum dispersions, often termed waterfalls, can occur at high energies in materials including nickelates and cuprates. Using dynamical mean-field theory, the authors show that these features naturally emerge when a Hubbard band develops and splits off from the central quasiparticle band.

The authors theoretically study the pressure dependence of the phase diagram of the nickelate PrNiO₂ with and without Sr doping. At high pressure, they find that the superconducting dome is significantly enhanced in both T_c and doping-range of superconductivity compared with ambient pressure, with a maximal T_c of 100 K around 100 GPa in absence of external doping.

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.

Current methods to generate sequence-function data at large scale are either technically complex or limited to specific applications. Here the authors introduce DNA-based phenotypic recording to overcome these limitations and enable deep learning for accurate prediction of function from sequence.

Substrate-specific proteases have an enormous potential in the life sciences, but tailoring their specificity remains challenging. Here, the authors describe a data-driven approach combining DNA recording and epistasis-aware deep learning to augment protease specificity engineering at large scale.

Here, the authors show that MacroD1 is important for mitochondrial integrity and function. Lack of MacroD1 resulted in impaired cellular respiration which was particularly detrimental for cells and organs with high energetic requirements, such as skeletal muscle.

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.

Understanding the silicon-oxygen system is crucial for various applications. Here, the authors present an interatomic potential covering a wide range of the Si-O configurational space and showcase applications to silica and Si-SiO2 interfaces.

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.

RNA of some viruses is protected from degradation by a 5′ triphosphate group. Here the authors identify nudix hydrolase 2 (NUDT2) as novel antiviral defense protein that dephosphorylates viral RNA and thereby enables its degradation.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

The ketone body β-hydroxybutyrate can be used as an alternative carbon source by T cells to maintain their function during severe respiratory viral infections, including infection with SARS-CoV-2.

The Micrarchaeota lineage includes poorly characterized archaea with reduced genomes that likely depend on host interactions for survival. Here, the authors report a stable co-culture of a member of the Micrarchaeota and its host, and use multi-omic and physiological analyses to shed light on this symbiosis.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

Shortened telomeres and reduced mitochondrial biogenesis are cellular hallmarks of ageing. Here, Missios et al.show that old mice with telomere dysfunction have an increased energetic demand that cannot be met unless mice are fed a glucose-rich diet, which improves energy metabolism and extends lifespan.

Solar photovoltaics is entering a multi-terawatt era, driven by decades of cost, performance and reliability gains. In this Perspective Alberi et al. discuss the role of historical and future learning, highlighting the increasing importance of sustainability considerations.

Revealing genetic influences on metabolic phenotypes is important in further understanding the aetiology of many complex diseases. Here, the authors introduce study design considerations and applications for genome-wide association studies with metabolic traits.

We classically consider the T cell compartment divided into cytotoxic CD8⁺ T cells and multiple, different helper CD4⁺ T cell subsets. Here the authors demonstrate that distinct memory CD8⁺ T cell subsets phenotypically inhabit CD4⁺ T cell like populations including some with helper-like characteristics.

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.

A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance.

The cryo-electron microscopy structure of human rhodopsin bound to the inhibitory G_i protein-coupled receptor provides insights into ligand–receptor–G-protein interactions.

T- and X-shaped polyphilic liquid crystals can generate ordered structures with potential nanotechnology applications. Here, the inability of polyphiles to achieve optimal packing and complete nanophase separation is exploited to produce a flexible two-dimensional honeycomb with giant octagonal and square cylinders.

The cytokinetic ring consists of actin and myosin, but their organisation prior to and during constriction has not been observed. Here the authors observe that mammalian and yeast cells organise their rings differently, with mammalian cells forming a periodic pattern of myosin clusters and yeast rotating myosin clusters during constriction.

Dislocations in high-entropy alloys encounter pinning during glide resulting in jerky motion. Here the authors demonstrate that the density of high local Peierls force is proportional to the critical stress required for their glide and mobility.

Researchers demonstrate a laser interferometer that achieves simultaneous nonclassical readout of two conjugated observables. Because their system uses steady-state entanglement, it does not require any conditioning or post-selection. By distinguishing between scientific and parasitic signals, its sensitivity exceeds the standard quantum limit by about 6 dB.

As indicated by direct band-structure measurements and calculations, tiny native imperfections in bilayer graphene are sufficient to cause the generation of coexisting massive and massless Dirac fermions. The massless spectrum is robust against strong electric fields and has a closed-arc topology consisting of a unique chiral pseudospin texture.

Connecting genomics and proteomics allows the development of more efficient and specific treatments for cancer. Here, the authors develop proteogenomic methods to defining cancer signaling in-vivo starting from core needle biopsies and with application to a HER2 breast cancer focused clinical trial.

The Parker spiral—arising from the interaction between the Sun’s magnetic field with the solar wind—is recreated in the laboratory from a rapidly rotating plasma magnetosphere.

Imprinting molecular memory on the surface of polymer nanoparticles creates artificial antibodies that can recognize and neutralize a toxic peptide in vivo.

In summer 2022 an enormous fish kill was observed in the Oder River as a consequence of prymnesins produced by an algal bloom. An investigation of the exposure of aquatic life and human cells to the contaminated Oder water revealed the presence of neurotoxicants, which are attributed to B-type prymnesins, with minor contributions by organic micropollutants.

Predicting nitrous oxide emissions (N₂O) remains difficult due to the numerous N₂O production pathways. Here, the authors use incubations simulating high nitrate inputs to show that, in intertidal sediments, increases in N₂O flux are largely mediated by fungal denitrification and/or chemodenitrification.

The Mouse Intestinal Bacterial Collection (miBC) is a public repository of bacterial strains and associated genomes from the mouse gut. A minimal consortium of 18 species covered 50–75% of the known functional potential.

G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling.

A bacterial strain that requires the neurotransmitter GABA for growth was identified and used to isolate GABA-producing bacteria, including Bacteroides spp., from human stool samples; the relative abundance of Bacteroides was negatively correlated with an altered GABA-mediated response in a depression patient cohort.

The mechanistic basis for the role of the metabolic enzyme BCAA transaminase 1 (BCAT1) in acute myeloid leukaemias.