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Results from the randomized, noncomparative, phase 2 MATISSE trial show that ultra-short neoadjuvant therapy with ipilimumab and nivolumab can prevent surgery and radiotherapy in patients with resectable cutaneous squamous cell carcinoma, with an early decrease in total lesion glycolysis by [¹⁸F]FDG-PET/CT associated with response.

A phase 3 trial found that VER-01, a full-spectrum cannabis extract, reduces chronic low back pain, improves physical function and sleep and shows no signs of dependence or withdrawal.

Decision-making in multi-agent systems often involves control goals that break reciprocity. Here, authors derive a field theory for such interactions, revealing nonreciprocal couplings that generate diverse collective behaviors through simple manipulations.

In the randomized phase 1b/2 Morpheus-Melanoma trial evaluating various neoadjuvant immune checkpoint inhibitor regimens in patients with resectable stage III melanoma, tobemstomig, an anti-PD-1/anti-LAG-3 bispecific antibody, showed the highest pathologic response rate with a better safety profile than the standard treatment approach of ipilimumab plus nivolumab.

Mauthe et al. find that protein aggregate clearance requires fragmentation of the aggregate by a chaperone module and a proteasomal regulatory particle for recruitment and clustering of selective autophagy receptors to initiate phagophore formation.

Cangkrama et al. show that tumor cells from various cancer types use the mitochondrial trafficking protein MIRO2 and nanotubes to transfer mitochondria into surrounding fibroblasts, thereby inducing cancer-associated fibroblast differentiation and subsequent tumor growth.

Uncovering the rules of microtubule network self-organization under confinement is key to understanding how cells build structure in complex environments. This study reveals a tunable boundary-sensing feedback mechanism, wherein pioneer microtubules navigate confined environments and generate nucleation sites for new microtubules, thereby shaping network architecture.

ProDomino is a machine leaning-based method, trained on a semisynthetic domain insertion dataset, to guide the engineering of protein domain recombination.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

There’s nothing intuitive about quantum theory — six physicists debunk some of the most common misconceptions.

On the basis of encouraging preclinical activity, an anti-CEACAM5 antibody–drug conjugate with a topoisomerase 1 inhibitor payload is being tested in an ongoing phase 1 trial where recommended doses for further testing have been identified and an unconfirmed overall response rate of 15% was observed in patients with metastatic colorectal cancer.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

The study introduces NXT2 as a candidate gene for male infertility and shows that the encoded protein is involved in RNA nucleocytoplasmic transport in human testis by interacting with the RNA export factor NXF1 and proteins of the nuclear pore complex. NXT2 also interacts with the human testis-specific NXF1 paralogues NXF2 and NXF3. Mutations in NXT2 and NXF3 are linked to a disruption of nuclear export, leading to defective germ cell development and human male infertility.

This study evaluates nitrogen surplus reduction scenarios across Europe using century-long sub-national data and a multidimensional clustering algorithm. The findings show that a 20% fertilizer reduction alone is insufficient to meet Farm to Fork targets and that region-specific strategies, combined with advances in technology and management practices, are essential.

Trumpp and colleagues develop a method to obtain long-term circulating tumor cell-derived organoids from individuals with metastatic breast cancer and identify the neuregulin 1–HER3 axis as important for organoid growth and a promising therapeutic target.

Impaired gut barrier function is a central driver of alcohol-related liver disease. This study indicates that the postbiotic ReFerm® improves gut barrier function and reduce liver stiffness and liver fibrosis, suggesting the gut barrier function as a potential treatment target.

The chromatin-remodelling enzyme ATRX and the transcription factor HNF4A are identified as pivotal regulators of colonic epithelial identity, with roles in metastasis in colorectal cancer.

Jovanovic et al. show that a gel-based diet can be used as a minimally invasive alternative system for the delivery of small molecules for microglia depletion and inducible Cre recombination in mice.

This study used AI to map ~29,000 CDR studies—3–4 times more than expected—showing rapid but uneven growth. The map supports stronger evidence synthesis for climate goals and the IPCC. #CDR

Livanos et al. provide mechanistic insight into the recruitment and maintenance of kinesin-12 POK2, a central component of the division site in plants that is required for cell plate positioning during cytokinesis.

Trinucleotide triphosphates act as both chaperones and as substrates for primer-free RNA synthesis by a polymerase ribozyme. They invade and maintain the single-stranded state of RNA strands, thereby overcoming a significant obstacle to prebiotic RNA copying and replication.

Analyses of 475 ancient horse genomes show modern horses emerged around 2200 bce, coinciding with sudden expansion across Eurasia, refuting the narrative of large horse herds accompanying earlier migrations of steppe peoples across Europe.

Routine breast MRI scans provide an opportunity to screen for thoracic aortic aneurysms, which are more fatal in women. Here, the authors show that a fully automated AI tool can screen for these aneurysms using routine breast MRI scans.

Sex and gender have been associated with differences in SARS-CoV-2 incidence and clinical outcomes and therefore warrant consideration in study designs. Here, the authors assess registered and published clinical COVID-19 studies and find that sex-disaggregated analyses are infrequently presented or planned.

The pathogen Pseudomonas aeruginosa uses a membrane complex, PelBC, to produce exopolysaccharides for biofilm formation. Here the authors combine structural analysis, simulations and single-channel recordings of PelBC to provide a detailed view on its unique architecture and dynamics, and reveal the export route for the polysaccharide.

A study presents archaeogenomic data for 131 individuals from 38 sites spanning 6,000 years, and details the demographic processes of the Caucasus and the surrounding steppe zone throughout the Bronze Age.

Although it has shown high efficacy in many tumor types, interleukin-12 (IL-12) treatment provokes severe systemic toxicity. Here, the authors discover that use of an IL-12Fc fusion cytokine with abolished binding to the neonatal Fc receptor presents efficacy in local glioblastoma therapy while preventing toxicity.

This study employs a citizen science approach to identify and classify over 230,000 light sources in German city centers, suburbs and villages. The results underscore the pivotal role of citizen science in expanding knowledge of artificial light emissions and bolstering policymaking efforts to mitigate urban light pollution.

Relaxosome is a complex involved in bacterial conjugation and the spread of antibiotic resistance genes. Using cryo-EM, the authors reveal how specific protein-DNA interactions within the relaxosome facilitate the transfer of plasmid DNA between bacteria.

Quantum interference in charge transport is attracting interest with applications in nanoelectronics and quantum computing. Here, the authors present a method for quantifying electronic transmission through molecules, and demonstrate constructive quantum interference in a molecule with two identical, parallel coupling paths.

Chimeric antigen receptor (CAR) T cells specific for an antigen, BCMA, have shown efficacy in controlling multiple myeloma in some patients, but responses vary. Here the authors show that, by over-expressing a granzyme B-NOXA fusion protein in anti-BCMA CAR T cells, cancer cells are rendered more susceptible to apoptosis induction and CAR T-mediated killing.

The study identifies the L704F mutation in Arabidopsis ABCG36 as a key factor that uncouples the export of the auxin precursor indole-3-butyric acid from the defense compound camalexin. It highlights L704 as a crucial residue in the extracellular gate that influences substrate identity and balances growth-defense trade-offs in the Brassicaceae family.

Alternative lengthening of telomeres (ALT) is associated with a poor outcome in neuroblastoma. Here, the authors find that ALT is associated with mutated ATRX and/or reduced protein abundance, frequent telomeric repeat loci and heterochromatic telomeric chromatin.

During mitosis, the chromatin undergoes a dynamic reorganization important for faithful chromosome segregation. Here the authors show that the DEAD-box RNA helicase eIF4A1/2 regulates the perichromatin layer’s composition required for chromatin decondensation during cell division.

A planet in a retrograde orbit around a star with a close-in white dwarf companion reveals the role of binary stellar evolution in the formation and evolution of planets.