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In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

In a phase 2 trial evaluating healthy donor fecal microbial transplantation plus either anti-PD-1 in patients with non-small cell lung cancer or anti-PD-1 and anti-CTLA-4 in patients with melanoma, encouraging efficacy was seen in both cohorts, with responses linked to significantly greater loss of baseline bacterial species.

Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Ribas and colleagues report the results of a phase 2 clinical trial of neoadjuvant PD-1 blockade in patients with surgically resectable desmoplastic melanoma.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

A single-cell epigenomic atlas of human immune cells highlights cell-type-specific features associated with genetic or environmental exposures.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

The ~500-metre-thick Prudhoe Dome in northwestern Greenland completely deglaciated 7,000 years ago, highlighting the sensitivity of the ice sheet to mid-Holocene warming, according to luminescence and geochemical data from sub-ice sediments and ice cores.

Endosomal sequestration of lipid-based nanoparticles is a barrier to delivery of nucleic acids. Here the authors test an array of cholesterol variants and perform in-depth investigation of nanoparticle shape, internal structure and intracellular trafficking.

Treatment-seeking for fever is widely used to estimate treatment of childhood infections, but cross-country comparisons are problematic. Here, the authors estimate the probability of seeking treatment for fever at public facilities across 29 countries by quantifying person-level latent variables.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

In a randomized phase 2 trial in patients with acute coronary syndrome and high levels of the inflammation biomarker C-reactive protein, treatment with low-dose interleukin-2 increased the numbers of regulatory T cells and reduced arterial inflammation, compared to placebo.

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

This study uses single-nucleus RNA sequencing to analyze lung tissue from 141 individuals with chronic obstructive pulmonary disease. Distinct patterns of spatially resolved changes in cell composition and cell states that correlate with clinical features are highlighted.

A Fab-IL-10 fusion protein that binds to LDL suppresses vascular inflammation in atherosclerotic mouse models.

Targeting histone deacetylases (HDACs) alone has shown limited success in solid tumours. Here, authors report that the HDAC1/2 inhibitor romidepsin confers responsiveness to receptor tyrosine kinase inhibitors, with enhanced therapeutic effects in models of hepatocellular carcinoma, leading to tumour regression and an immune-stimulatory profile.

Utricle, a component of the inner ear vestibular system, is essential for balance. This study maps the cells and genes in the adult human utricle. It identifies distinct non-sensory cell types and reveals early responses to damage, providing insight into potential strategies for restoring balance.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

Results from the phase ELAD 2 trial reveal that liraglutide is safe and well tolerated in people with mild to moderate Alzheimer’s disease but does not significantly slow brain metabolism decline.

Reduced GC-related content in the influenza A virus genome may be a necessary condition for sustained mammalian transmission and should be included in risk assessment tools for pandemic influenza.

In this Expert Recommendation, a working group integrating diverse perspectives presents a comprehensive overview of the clinical relevance and applicability of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the rationale for its use as an outcome measure in clinical trials, addressing a long-standing roadblock in the development of new drugs for CLE.

Initiating aripiprazole antipsychotic monotherapy versus olanzapine, quetiapine or risperidone might reduce cardiovascular event risk in severe mental illness. Here, the authors show patients initiating aripiprazole had similar 5-year risk as the comparators, but risk was higher in those continuing risperidone versus aripiprazole

High-resolution flare footpoint observations in the extreme ultraviolet and X-rays were taken by Solar Orbiter. Combined with simulations, the results reveal that the dominant mechanism carrying flare energy through the Sun’s atmosphere can vary on small spatial scales.

Kang, Lazo de la Vega et al. introduce iCatalog, a precision oncology reporting tool developed to address the needs of a large multi-institutional pediatric study. iCatalog combines a database for patient, sample, and genomic data to enable clinical interpretation of patient-level tumor profiling results.

Here, the authors find that a benign polygenic predisposition to lower white blood cell counts is associated with multiple clinical endpoints, suggesting that predisposed individuals are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.

In a trial involving 45 clinics and 15,596 visits, the use of an AI-based screening tool applied to ECG for opportunistic detection of advanced chronic liver disease led to a significant increase in new diagnoses compared to the standard workflow.

Neutrophil-derived IL-1β has a role in preserving lipid stores during metabolic stress.

Neonatal brain injury from intermittent hypoxemia increases fatty acid oxidation and causes long-term changes in hippocampal lipid profile. Here authors demonstrate oral treatment with glycerol-triacetate restores lipid fatty acid profile and promotes functional recovery.

Liu and colleagues demonstrate that biomimetic fractal patterns derived from glomerular histology can enhance the maturation of podocytes (highly differentiated glomerular cells) that are grown in culture. This work presents a bioengineered platform for improved cell culture fidelity.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

A deep-learning-based de novo design strategy was developed that enables simultaneous scaffolding of three distinct epitopes derived from respiratory syncytial virus within small single-domain immunogens. Crystallographic analyses confirmed precise presentation of the designed motifs. The multiepitope constructs elicited enhanced cross-reactive and neutralizing antibody responses, demonstrating the potential of generative models for complex multisite protein engineering.

In this study, Yu et al. found that a positive feedback loop between oxidized phosphatidylcholine and IL-1β promotes chronic neurodegeneration in the central nervous system and could be a contributing mechanism to progressive multiple sclerosis.

Distinct endocannabinoids signal to either astrocytes or neurons, evoking contrasting regulation of synaptic function. This works reveals the high degree of complexity of neuronal and astrocytic signaling in brain function.

Temperature-dependent host–pathogen interactions may lead species to shift their thermal preferences under pathogen pressure. However, here the authors show that bats have not altered their microclimate preferences due to temperature-mediated mortality from white-nose syndrome, finding instead a sustained preference for warmer sites with high mortality.