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Breaking Agent Backbones: Evaluating the Security of Backbone LLMs in AI Agents
Progressive Growing of Patch Size: Curriculum Learning for Accelerated and Improved Medical Image Segmentation
Integrated epigenetic and genetic programming of primary human T cells
Nature Biotechnology, Published online: 21 October 2025; doi:10.1038/s41587-025-02856-w
Multiplexed editing in primary human T cells generates enhanced immune cell therapies.Parity and lactation induce T cell mediated breast cancer protection
Nature, Published online: 20 October 2025; doi:10.1038/s41586-025-09713-5
Parity and lactation induce T cell mediated breast cancer protectionAlternatives to animal testing are the future — it’s time that journals, funders and scientists embrace them
Nature, Published online: 20 October 2025; doi:10.1038/d41586-025-03344-6
Biomedical research techniques that don’t involve the use of animals are gaining momentum, but those using innovative approaches still face resistance from some quarters.Evidence of fructose metabolism in colorectal cancer
Cell Death Discovery, Published online: 16 October 2025; doi:10.1038/s41420-025-02745-w
Evidence of fructose metabolism in colorectal cancerFramework for the Development and Delivery of Digital Peer Support Programs: Qualitative Study on in-Person and Digital Delivery for People With Cardiovascular Disease
A human pan-disease blood atlas of the circulating proteome
Stripe enlists a who’s who, including Anthropic, OpenAI, and Paradigm, to build a new blockchain
An eyecare foundation model for clinical assistance: a randomized controlled trial
Nature Medicine, Published online: 28 August 2025; doi:10.1038/s41591-025-03900-7
Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.GeneBits: ultra-sensitive tumour-informed ctDNA monitoring of treatment response and relapse in cancer patients
J Transl Med. 2025 Aug 27;23(1):964. doi: 10.1186/s12967-025-06993-3.
ABSTRACT
BACKGROUND: Circulating tumour DNA (ctDNA) in liquid biopsies has emerged as a powerful biomarker in cancer patients. Its relative abundance in cell-free DNA serves as a proxy for the overall tumour burden. Here we present GeneBits, a method for cancer therapy monitoring and relapse detection. GeneBits employs tumour-informed enrichment panels targeting 20-100 somatic single-nucleotide variants (SNVs) in plasma-derived DNA, combined with ultra-deep sequencing and unique molecular barcoding. In conjunction with the newly developed computational method umiVar, GeneBits enables accurate detection of molecular residual disease and early relapse identification.
RESULTS: To assess the performance of GeneBits and umiVar, we conducted benchmarking experiments using three different commercial cell-free DNA reference standards. These standards were tested with targeted next-generation sequencing (NGS) workflows from both IDT and Twist, allowing us to evaluate the consistency and accuracy of our approach across different oligo-enrichment strategies. GeneBits achieved comparable depth of coverage across all target sites, demonstrating robust performance independent of the enrichment kit used. For duplex reads with ≥ 4x UMI-family size, umiVar achieved exceptionally low error rates, ranging from 7.4×10-7 to 7.5×10-5. Even when including mixed consensus reads (duplex & simplex), error rates remained low, between 6.1×10-6 and 9×10-5. Furthermore, umiVar enabled variant detection at a limit of detection as low as 0.0017%, with no false positive calls in mutation-free reference samples. In a reanalysed melanoma cohort, variant allele frequency kinetics closely mirrored imaging results, confirming the clinical relevance of our method.
CONCLUSION: GeneBits and umiVar enable highly accurate therapy and relapse monitoring in plasma as well as identification of molecular residual disease within four weeks of tumour surgery or biopsy. By leveraging small, tumour-informed sequencing panels, GeneBits provides a targeted, cost-effective, and scalable approach for ctDNA-based cancer monitoring. The benchmarking experiments using multiple commercial cell-free DNA reference standards confirmed the high sensitivity and specificity of GeneBits and umiVar, making them valuable tools for precision oncology. UmiVar is available at https://github.com/imgag/umiVar .
PMID:40866952 | PMC:PMC12382282 | DOI:10.1186/s12967-025-06993-3
Integrative genomic identification of therapeutic targets for pancreatic cancer
Cell Rep. 2025 Aug 21;44(9):116191. doi: 10.1016/j.celrep.2025.116191. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and new therapeutic strategies are urgently needed. Here, we conduct an integrative, genome-scale examination of genetic dependencies and cell surface targets using CRISPR-Cas screening and multi-omic data, including single-nucleus and spatial transcriptomic data from patient tumors. We systematically identify clinically tractable and biomarker-linked PDAC dependencies, including CDS2 as a synthetic lethal target in cancer cells expressing signatures of epithelial-to-mesenchymal transition. We examine biomarkers and co-dependencies of the KRAS oncogene, defining gene expression signatures of sensitivity and resistance associated with response to pharmacological inhibition of KRAS. mRNA and protein profiling reveal cell surface protein-encoding genes with robust expression in patient tumors and minimal expression in non-malignant tissues. Furthermore, we define intratumoral and interpatient heterogeneity of target gene expression and identify orthogonal targets that suggest combinatorial strategies. Collectively, this work identifies multiple targets that may inform therapeutic strategies for patients with PDAC.
PMID:40848256 | DOI:10.1016/j.celrep.2025.116191
Raising multiple rounds of venture capital might be wrong for your startup
Recent advances in liquid biopsy for precision oncology: emerging biomarkers and clinical applications in lung cancer
Future Oncol. 2025 Aug 5:1-19. doi: 10.1080/14796694.2025.2542051. Online ahead of print.
ABSTRACT
Lung Cancer (LC) remains the leading cause of cancer-related mortality. While Tissue Biopsy (TB) remains the gold standard for molecular profiling, its invasiveness and inability to provide real-time monitoring have led to the adoption of Liquid Biopsy (LB) as a minimally invasive alternative. By analyzing different circulating analytes such as cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), Circulating Tumor Cells (CTCs), Extracellular Vesicles (EVs), and Tumor-Educated Platelets (TEPs), LB offers a dynamic approach to assessing tumor heterogeneity, Minimal Residual Disease (MRD), and treatment resistance. Recent clinical trials have underscored their role in guiding therapy decisions and monitoring treatment response. In early-stage disease, several Randomized Clinical Trials (RCTs) have shown that ctDNA clearance predicts survival benefits in patients receiving neoadjuvant or perioperative Immune Checkpoint Inhibitors (ICIs). Additionally, adjuvant RCTs have confirmed the ctDNA prognostic role in post-surgical relapse risk assessment. Despite its transformative potential, challenges such as assay standardization, sensitivity limitations in early-stage disease, and regulatory barriers remain. As ongoing research continues to validate its clinical utility, LB is poised to become an indispensable tool in the precision management of LC.
PMID:40762271 | DOI:10.1080/14796694.2025.2542051
Nanobody therapy rescues behavioural deficits of NMDA receptor hypofunction
Nature, Published online: 23 July 2025; doi:10.1038/s41586-025-09265-8
A bivalent biparatopic nanobody penetrates the brain, binds to and potentiates the activity of homodimeric metabotropic glutamate receptor 2, correcting cognitive deficits in two preclinical mouse models with endophenotypes resulting from NMDA receptor hypofunction.ChatGPT is testing a mysterious new feature called ‘study together’
Human embryo research: how to move towards a 28-day limit
Nature, Published online: 01 July 2025; doi:10.1038/d41586-025-02016-9
The decades-old limit on how long human embryos can be grown in culture is under debate. A new road map outlines how to extend the length of culture responsibly.Chime almost died in 2016, turned down by 100 VCs — today it IPO’d at $14.5B
Biomarkers in adjuvant and neoadjuvant treatment of melanoma
Dermatologie (Heidelb). 2025 Jun;76(6):361-364. doi: 10.1007/s00105-025-05506-z. Epub 2025 May 7.
ABSTRACT
BACKGROUND: Personalized treatment of melanoma is becoming increasingly more important. Biomarkers offer the possibility of controlling treatment more precisely and reducing side effects.
OBJECTIVE: The aim of this text is to provide an overview of current tissue-based, blood-based and radiological biomarkers and their clinical application in melanomas.
MATERIAL AND METHODS: A literature research and analysis of current studies on biomarkers in adjuvant and neoadjuvant treatment of melanomas were carried out and relevant congress contributions were additionally included.
RESULTS: Tissue-based programmed cell death 1 ligand 1 (PD-L1) expression, interferon gamma (IFNγ) signature, gene expression profiles (GEP) and tumor mutational burden (TMB) are of prognostic and predictive relevance. Blood-based circulating tumor DNA (ctDNA) in the sense of a liquid biopsy should be emphasized as a personalized biomarker for longitudinal tracking during treatment or aftercare. Positron emission tomography computed tomography (PET-CT) and body composition enable an improved assessment of treatment efficiency. There are currently no data from prospective validation studies on these biomarkers; initial data from the NivoMela study are awaited.
CONCLUSION: The combination of tissue-based, blood-based and radiological biomarkers in terms of multiparametric approaches is promising but further prospective validation is needed for broad clinical use. These are currently not comprehensively implemented in the clinical routine in centers or in remuneration procedures.
PMID:40335648 | DOI:10.1007/s00105-025-05506-z