Search

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.

Semaglutide, a GLP-1 receptor agonist, may offer neuroprotective benefits after stroke, but its effects in large vessel occlusion (LVO) are unknown. Here the authors show, in a phase 2 randomized trial, that semaglutide is safe after endovascular therapy and may improve recovery in patients not receiving intravenous thrombolysis.

Lewis acid catalyzed tittle reaction of 1,3-dicycloalkenlidine ketones is recognized as so far the shortest and most effective 1-step method for construction of angular tricyclic scaffolds, which are extensively found in bioactive terpenoids. Here, the authors disclose the structure-reactivity relationship and a regioselectivity predicting model based on in situ IR technology, DFT calculations and machine leaning algorithms.

In nasopharyngeal carcinoma (NPC), cisplatin is known to be associated with poor treatment compliance and notable side effects therefore more effective platinum drugs are expected. Here this group updates the 10-year survival analysis results of a multicenter, randomized, phase 3 trial evaluating the efficacy of lobaplatin and fluorouracil induction chemotherapy plus concurrent chemoradiotherapy on 502 NPC patients.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

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 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.

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

METTL3 promotes healthy placenta function by regulating m⁶A methylation and histone epigenetics. Deficiency in METTL3 leads to premature senescence, inflammation activation of trophoblasts, contributing to pregnancy complications like preeclampsia.

Mutations of the histone H3K36-specific methyltransferase ASH1L have been linked to several human diseases. Here, the authors report the mechanism by which three C-terminal domains in ASH1L regulate its enzymatic activity and interact with chromatin.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

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.

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.

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.

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.

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.

Authors present a bispecific antiviral design targeting the virus and the host that simultaneously offers broad-spectrum protection against multiple existing transmissible human-pathogenic coronaviruses, including the Paxlovid-resistant SARS-CoV-2 mutants.

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.

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 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.

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.

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.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Smad3, a transcription factor activated by TGF-β, has been implicated in tumorigenesis. Here the authors show that Smad3 inhibits NK cell differentiation and effector function by repressing NFIL3, and that genetic or pharmacological blockade of Smad3 expands tumour-suppressive NK cells and restricts tumour growth in mice.

In the CheckMate 142 study, nivolumab (anti-PD-1) alone and in combination with ipilimumab (anti-CTLA-4) was shown to induce durable clinical benefit in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. Here, the authors perform exploratory biomarker analysis of the CheckMate 142 study.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

There is still no consensus on tumour type-specific cancer stem cell markers. Here, the authors demonstrate that ITGA7 is a potential functional marker of oesophageal cancer stem cells involved in the resistance to chemotherapy and metastasis through activation of FAK-mediated signalling.

ARF4 GTPase activity is needed for vesicular trafficking for multiple RNA viruses. Blocking ARF4 using specific peptides redirects viral progeny to lysosomal degradation and decreases influenza and Zika virus infection in mice.

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

Identifying optimal personalised strategies for neoadjuvant therapy in breast cancer remains an important challenge. Here, the authors develop GDnet, a deep learning model that uses drug representations and tumour transcriptome profiles to predict the response to neoadjuvant therapy in breast cancer patients, aiding in the optimisation of treatment strategies.

Increasing evidence suggests that activation of oncogenic pathways contributes to an unfavorable tumor microenvironment. Here, the authors show that wild-type KRAS plays a key role in immune evasion in hepatocellular carcinoma by impairing interferon-mediated immunity and promoting resistance to immunotherapy via the EGFR/MEK/ERK pathway.

Here, the authors show that a single mutation in JN.1 spike, L455S, confers better spike cleavage and enhances virus infectivity in differentiated primary human nasal epithelial cells while increasing immune evasiveness, contributing to the efficient spread of JN.1.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Influenza A viruses spread through contact, large and small respiratory droplets (aerosols), but the relative importance of these modes of transmission is unclear. Cowling et al. model data from community trials of face masks and hand hygiene and find that aerosol transmission accounts for half of influenza occurrences.

Difficulties in propagating HRV-C have hindered our understanding of this common respiratory pathogen. Here, authors developed an organoid-based system to reproducibly propagate HRV-C and characterized HRV-C infection in physiologically active respiratory organoids.