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Chen, Cai et al., present a rigorous human-in-the-loop framework for evaluating the medical performance of AI-generated responses to real clinical questions, using a scale aligned with physician career stages. Although some models perform at levels comparable to early-career physicians, substantial rates of incompetent answers and hallucinations demonstrate that unmonitored clinical deployment remains risky, underscoring the continuing need for expert oversight.

A dual-action force dynamics strategy using a hard silicon template as a nanoimprinting stamp combined with inverted transfer printing is described for the manufacture of high-performance full-colour ultrahigh-resolution quantum dot light-emitting diodes (LEDs) for active-matrix displays, while revealing electric-field reconstruction in nanoscale arrays and introducing dielectric matching to mitigate field concentration and performance degradation.

Chirality has long fascinated chemists, but asymmetric synthesis has largely focused on central, axial, and helical chirality to date. Here, the authors synthesize dianthranilides with planar chirality, via cinchona alkaloid-catalyzed (dynamic) kinetic resolution.

Dysregulation in proteolysis contributes to brain tumorigenesis. Here the authors report that USP10 deubiquitinase is enriched in glioma stem cells (GSCs), which antagonizes DTX3L-mediated ubiquitination of SATB2, a major driver of GSC proliferation and self-renewal.

Reactive oxygen species induced by endoplasmic reitculum stress can be exploited for cancer therapy. Here, nanoparticles are targetted to the endoplasmic reticulum and, when accompanied by PDT, produce stress resulting in calreticulin exposure on the cell surface, which activates dendritic cells.

Genomic, transcriptomic and metabolomic analyses from a population of 295 diverse sweet-corn inbred lines provide insights into kernel quality formation mechanisms and the divergence of sweet corn and field corn.

The Oryza genus comprise two cultivated rice species and 20 extant wild species. Here the authors assemble genomes of 13 representative wild rice species, construct a super pangenome by integrating them with four previously reported genomes in the genus, and reveal the genome evolution and diversity within the genus.

New study shows forests with ectomycorrhizal strategies accumulate more carbon stocks than forests dominated by arbuscular mycorrhizal or mixed mycorrhizal strategies in high-latitude.

This trial evaluated the immunogenicity and safety profiles of a bivalent aerosolized adenovirus-vectored COVID-19 vaccine and an intramuscular bivalent mRNA booster. The mRNA booster induced higher neutralizing antibody levels and a distinct memory B cell response, yet was associated with a higher incidence of adverse reactions.

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.

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.

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.

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.

Systemic drug delivery to the bone marrow is limited, currently requiring high doses of drug, increasing the risk of side effects. Here, the authors report on the hitchhiking of drug nanoparticles in neutrophils using their natural homing to the bone marrow for targeted delivery, and demonstrate its application.

Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, which correlate with excessive ROS and hyperactivated XBP1. Here, the authors introduce KT-NE, a nanoemulsion combining KIRA6 (an XBP1 inhibitor) and α-Tocopherol, easing ER and oxidative stress in (pre)adipocytes and showing anti-obesity effectiveness.

A cross-ancestry GWAS meta-analyses of brainstem structures identify 713 associations. It reveals shared/distinct genetic architectures across ancestries/substructures and overlaps with neuropsychiatric disorders and physiological functions.

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.

Tryptophan plays important biological roles in aromatic cages, such as methyllysine recognition, but the development of site-selective crosslinking to tryptophan is challenging. Now sulfonium can be used as a methyllysine mimic that binds to reader proteins and crosslinks tryptophan inside a pocket through single-electron transfer. This strategy enables the identification of methyllysine readers from the proteome.

Though DNA framework-based scaffolds for biomolecular assembly are attractive for bioimaging applications, realizing super-multiplex fluorescent amplifiers remains a challenge. Here, the authors report a topological engineering approach to designing fractal DNA frameworks for multiplexed amplifiers.

Only one of the three Taenia species causing taeniasis in humans was previously sequenced. Here the authors provide draft genomes of Taenia saginata and Taenia asiatica, analyse genome evolution of all three species, and identify potential targets for developing diagnostic markers or intervention tools.

Any TFs other than OCT4 that can individually induce the formation of mouse iPSCs are currently lacking. Here, Xiao et.al. report a single-SALL4-mediated somatic reprogramming method and reveal the underlying mechanism of this process.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

The authors integrate spatial (Stereo-seq) and single-cell transcriptomes of the developing maize ear to produce an atlas of maize ear cells and their developmental trajectories. They also identify a pair of transcription factors involved in inflorescence development.

The mechanism driving inflammatory-to-proliferative state transition during wound healing remains unclear. Here, the authors discover that SNHG26 interacts with ILF2, redirecting it from inflammatory genomic loci to the LAMB3 locus, thereby promoting wound healing.

The molecular mechanisms underlying the late-onset adverse effects of radiotherapy remain to be explored. Here, the authors observe compromised wound healing capacity in irradiated skin from breast cancer survivors and highlight THBS1 as a key epigenetically primed wound repair-related gene.

COVID-19 is a critical public health threat, but molecular characterizations of patients’ immunity is still lacking. Here the authors collected blood from patients with various disease severity, and prefiltered to exclude selected comorbidity, to obtain genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles to report a trans-omics landscape.