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New method can help guide treatment with most effective antibiotic — plus how things get weird when an AI is trained on AI-created text.

Restructuring of genome sections creates conditions that increase blood cancer risk — plus, the latest from the Nature Briefing.

We round up some recent stories from the Nature Briefing.

Neurons in medial entorhinal cortex collectively represent discrete nonlocal positions during immobility. During this nonlocal coding, CA1 is uncoupled from entorhinal cortex. These representations are of task-relevant locations.

A new optical imaging study demonstrates that norepinephrine and the state of arousal influence hemodynamic correlations across cerebral cortex, calling for a conceptual shift in interpreting functional magnetic resonance imaging data.

Preclinical studies have evaluated murine double minue 2 (MDM2) inhibitors as a treatment for adenoid cystic carcinoma (ACC). Here the authors present a phase I clinical trial reporting tolerability and efficacy preliminary data for the MDM2 inhibitor alrizomadlin (APG-115) in patients with TP53 wild type salivary gland cancers, especially adenoid cystic carcinoma.

In the wake of devastating floods in the South of Brazil, researchers are working out how best to help people — plus, what concerns do Nature’s readers have about the US election.

Mitochondria divide to share the load when nutrients are scarce — plus, how smashing atomic nuclei together helps identify their shapes.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

With a combined length of 23 million light years, these jets are the biggest yet discovered — plus, a single-step process for making metal alloys.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusion.

Lipid nanoparticles incorporating a crosslinked ionizable lipid are shown to promote efficient endosomal escape of antigen mRNA and glycolysis stimulation in dendritic cells, to elicit robust vaccination against viruses and cancer.

In this phase 1, open-label dose-escalation study in healthy adults found that the mRNA vaccine (mRNA-1215), encoding the Nipah virus Malaysian strain chimeric pre-fusion F protein linked to glycoprotein G, was safe and induced elevated immune responses at 1 year of follow-up, indicating that this is a promising vaccine candidate for further development.

Catabolism of extracellular glutathione by γ-glutamyltransferases supports tumour growth and survival, and pharmacological targeting of these enzymes slows tumour growth.

Hodgson, Huang, Lang et al. show that TDP-43 limits ribonucleoprotein particle condensation into paraspeckles in a concentration- and polymerization-dependent manner. They also link paraspeckle condensation to stress response and neuroprotection.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

The phase 2/3 DEVOTE trial demonstrated that high-dose nusinersen significantly improved motor function and was safe in patients with spinal muscular atrophy, compared with a matched sham control.

Conventional type 1 dendritic cells (cDC1) can boost the precursor exhausted T cell population thought to be essential for efficacy of immune checkpoint therapy. Here the authors enhance this cellular network using Flt3L to expand cDC1s and then map the movement of T cells and DCs between tumors and lymph nodes.

An intracellular protein-based recorder called CytoTape is capable of tracking cell activities over weeks and at scale.

A lipid nanoparticle that delivers mRNA encoding for regenerative factors to the endometrium with high specificity restores implantation rates in a murine model of endometrial injury with potentially improved safety.

Germline and somatic interactions define actionable genomic patterns driving acquired therapy resistance in breast cancer.

Here authors show that the function of prefrontal cortex, an area that controls executive function and cognition, is impaired on a cellular and network level in mice born preterm.

Allcott et al. conducted an experiment in 2020, removing political ads from the feeds of randomly selected Facebook and Instagram users. There were no statistically significant effects on political outcomes such as knowledge, polarization and turnout.

This work describes three people living with HIV-1 who maintain long-term immune-mediated control of HIV-1 after pausing antiretroviral therapy. Autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4⁺ and CD8⁺ T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. This serves as a model of ART-free control of HIV-1 and informs new HIV-1 cure strategies.

The study shows that vaccination with two doses of recombinant zoster vaccine is associated with a 51% reduction in the risk of dementia in adults aged ≥65 years. Reduction in risk is comparable across subgroups and remains statistically significant after accounting for healthy vaccinee bias.

To write this article, the authors, members of the International Women in Supramolecular Chemistry (WISC) network surveyed colleagues who care for older children about the challenges of integrating that role with their academic careers.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

Simulated heatwaves shifted carbon fluxes in estuarine flats, with stronger effects after longer heatwave durations. Findings reveal that degradation state will influence heatwave effects on carbon dynamics including changes in source/sink status.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Endosomal escape of lipid nanoparticles is quantified and optimized in vivo.

In a study of four brain-dead human decedents, extracorporeal liver cross-circulation using genetically modified pig livers provides essential hepatic functions, supporting the feasibility of this approach for temporary liver support as a bridge to organ transplantation.

The factors contributing to the onset of Barrett’s esophagus, a precancerous stage of the highly lethal esophageal cancer, remain elusive. Here, the authors identify inherited mutations in the VSIG10L gene as a key etiologic determinant affecting esophageal biology and facilitating the development of Barrett’s esophagus.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Endothelial-to-mesenchymal transition contributes to plaque progression in atherosclerosis. Here, Ayllon et al. show that the protein TWIST1 drives endothelial cell plasticity in atherosclerosis, promoting plaque growth and stability while reducing features linked to rupture, challenging the view that these cell changes always worsen disease.

Chen et al. assessed the prevalence and risk factors for treatment-resistant postpartum depression using nationwide data from the Swedish National Medical Birth Register.

The authors identify pathogenic variants in the SMARCA1 gene as the cause of a variable neurodevelopmental disorder. Mouse studies suggest diverse genetic mechanisms related to NURF complex composition mediate the phenotype.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

IL-17A, a cytokine important for tissue repair, can impair healing when increased, contributing to keratinocyte dysfunction in type 2 diabetic wounds. Here, the authors show that IL-17A drives this dysfunction via JMJD3-mediated epigenetic changes, and that blocking this pathway improves wound healing.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Allogenic mesenchymal stem cells are engineered with three mRNAs to bind to multiple myeloma B cells while activating T cells for cancer therapy.

In this study, the authors show that integrating a host gene biomarker with a large language model (LLM) improved lower respiratory tract infections diagnosis in a cohort of critically ill patients. The LLM plus biomarker outperformed the diagnosis made by the initial medical team and each component alone.

Large-scale combinatorial perturbation screens are important to identify genetic interactions and synthetic lethal gene pairs. Here, Burgold et al. present a next-generation dual guide system that allows library-scale screening across hundreds of thousands of genetic interactions.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Mesocosm experiments revealed that both phytoplankton community composition and cellular acclimation influence marine particulate C:N:P ratios, with community shifts more sensitive to nitrogen supply and acclimation to the nutrient N:P supply ratio

Ni, Wei, Vona and colleagues use human brain organoids to dissect patient AIRIM variants associated with neurodevelopmental features. A subset of variants impaired ribosome production and protein synthesis, and delayed radial glial cell specification.

Here, the authors show that myoferlin is a crucial host factor that helps move viral genetic cargo to the cell surface, boosting influenza, RSV and Sendai virus spread, highlighting a common weak spot for future antivirals.