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Systemic autoinflammatory disorders (SAID) represent a heterogeneous family of immune dysregulation disorders with overlapping clinical characteristics, making a precise and timely diagnosis challenging. Here, the authors collect samples from a group of patients diagnosed with autoinflammation of unknown origin, and by combining immunophenotyping, plasma proteomics, and machine learning, identify key immunological drivers of this condition with a signature that partially overlaps that of Still’s disease.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

By integrating liquid biopsies and tissue signatures, this study characterizes giredestrant response in ER+ breast cancer. The findings show that multimodal biomarker profiling can predict clinical benefit and personalize endocrine therapy.

A global analysis of 1,412 studies shows that one in five women and one in six men experienced sexual violence as children, highlighting the urgent need for evidence-based prevention and intervention programmes worldwide.

Here, the authors propose the Antarctic Ecosystem Value Index, an Earth systems model-based measure of marine ecological value. The index identifies potential present and future high-value locations, which often fall within coastal polynyas.

In a randomized trial enrolling Black adults residing in food deserts in Boston, Massachusetts, who were undergoing treatment for hypertension, home-delivery for 3 months of groceries designed to provide a low-sodium diet, together with dietician counseling, reduced blood pressure beyond a monetary stipend, an effect that was maintained for an additional 3 months after the intervention ended.

The authors simulate phytoplankton macromolecular composition—proteins, carbohydrates and lipids—under present and future scenarios. They show increased protein allocation in subtropical phytoplankton but declines in high-latitude populations under warming, with implications for marine food webs.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

A multiplexed RNA detection method exploits crRNA-dependent variability in Cas13a activity on RNA targets for kinetic barcoding and can be used to distinguish among SARS-CoV-2 variants in clinical samples.

The first-in-human clinical trial of the LRRK2-targeting antisense oligonucleotide BIIB094 in Parkinson’s disease demonstrates that the treatment is well tolerated and produces dose-dependent reductions in cerebrospinal fluid levels of LRRK2 and phosphorylated Rab10, indicating successful target engagement.

This study presents an organ-wide spatial transcriptomic analysis of human skin from different anatomical sites using a combination of MERFISH technology and existing datasets from healthy and diseased skin.

Over five years, implementation of the NHS England Lung Cancer Screening Programme achieved high early-stage detection rates and demonstrated that the programme is both feasible and scalable for reaching high-risk and underserved populations.

Raam, Li, Gu and colleagues identify neural mechanisms underlying group huddling in mice during cold exposure. They find that the prefrontal cortex encodes decisions to huddle and that silencing neural activity in some animals causes partners to compensate in response.

Nesbeth et al. use metabolome-wide association studies to identify newborn metabolic profiles associated with prenatal tobacco exposure and early birth. Results reveal changes in biopterin metabolism as a potential link between prenatal tobacco exposure and early birth.

Annotating regulatory elements in domestic animal genomes is important to understand the mechanisms underlying gene regulation. Here, the authors use multi-omics data from sheep to map regulatory elements in the sheep genome.

Jakubzick and colleagues show that the tumor microenvironment is shaped by opposing programs in tissue-resident CD206^hi and CD206^lo interstitial macrophages and Ly6c2⁺Fn1⁺Vcan⁺ recruited macrophages, various macrophage subsets that are spatially segregated and mechanistically distinct.

The mechanisms of increased EPAS1 transcription in clear cell renal cell carcinoma remain to be explored. Here, the authors propose a regulatory circuitry of EPAS1 expression which is dependent on HIF and lineage-specific transcription factors.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Gut microbial changes promoted by weaning in mice result in epigenetic modification in intestinal stem cells with long-lasting impact on host immunity.

This scoping review highlights the potential of mobile and wearable technologies for continuous monitoring of depressive symptoms. Analyzing 52 studies, it identifies key predictive features and demonstrates that personalized models substantially enhance accuracy in just-in-time depression prediction.

Here the authors perform an epigenome-wide DNAm study in 472 AD brains, identifying 5,478 regional methylation associations, mainly with tau. Replication and integration analyses reveal 93 regions and 535 genes enriched in oligodendrocyte genes, a subset of which were consistent across tauopathies.

T-prolymphocytic leukemia (T-PLL) is an aggressive T-cell malignancy, but 15–25% of cases are diagnosed at a primarily indolent stage. Here, the authors use single-cell RNA sequencing and whole genome sequencing to study the molecular changes underlying the indolent-to-active evolution of T-PLL, finding patient-specific and common mechanisms of disease progression.

Genomic and transcriptomic profiling reveals divergent clonal evolution and TME remodeling in gastric cancer peritoneal metastasis, highlighting substantial heterogeneity and the need for metastasis-specific therapeutic strategies.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

XCR1+ type 1 conventional DCs (cDC1s) are crucial to mount anti-tumor immune responses, however their infiltration within tumours is often limited. Here the authors show that cDC1 infiltration could be expanded by intratumoral delivery of mesenchymal stromal cells engineered to express the membrane bound form of FLT3L in combination with poly(I:C) or CXCL9 and CCL5, improving anti-tumor immunity in preclinical models.

The secondary neuroinflammatory immune response determines the overall clinical outcome after traumatic brain injury (TBI). Here, the authors show in a mouse TBI model that NF-kB activation in astrocytes is a pathological mechanism limiting beneficial CNS wound healing.

The mosquito fat body plays key roles in metabolism and immunity. Here, using single-nuclei transcriptomics the authors reveal that blood feeding induces extensive transcriptomic changes, endoreplication and metabolic shifts in fat body trophocytes, while oenocytes respond to immune priming.

Oxytocin promotes social behaviors, but its cortical targets remain unclear. Here, authors show that oxytocin activates local interneurons in the rat prefrontal cortex, enhancing sociability through top-down control of the basolateral amygdala.

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.

In this study, long-read RNA sequencing achieves accurate single-nucleotide polymorphism calling, haplotype phasing and allele-specific expression analysis.

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.

Elevated serum levels of phosphorylated tau are not specific to Alzheimer’s disease and may also serve as a diagnostic tool for the most common types of systemic amyloidosis, with potential utility in distinguishing amyloidosis-related polyneuropathy from polyneuropathy of other etiologies.

Restoring ecosystems depends on the cultivation of native plants to balance biodiversity with agricultural needs. This Letter finds that despite being overlooked for commercial varieties, 85% of Mediterranean native annuals could be used in olive groves for nature-based agronomy.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Glucocorticoid receptor activation is a key driver of resistance of triple-negative breast cancer to both CD8⁺ T cells and natural killer cells during initial metastatic seeding.

Coastal and marine projects in the Global South can exacerbate existing contextual inequities, particularly in high-stakes locations found across all ocean basins and identified using current investment levels and a composite index of inequity.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Here the authors compare genetic testing strategies in rare movement disorders, improve diagnostic yield with genome analysis, and establish CD99L2 as an X-linked spastic ataxia gene, showing that CD99L2–CAPN1 signaling disruption likely drives neurodegeneration.

The authors model the emergence of climate-driven changes in Antarctic sea ice, phytoplankton, krill, fish and penguins. They show earlier emergence for higher trophic levels, as well as highly seasonal and regional responses.

Neurotrophic factor Nerve Growth Factor (NGF) is involved in bladder physiopathology. Here the authors report that mast-cell derived NGF sustains the pro-tumoral functions of ILC2s in bladder cancer (BC), showing that selective targeting of the NGF receptor TrkA improves survival and response to immune checkpoint blockade in BC models.

The recruitment of RNAPII to gene promoters is initiated by TBP and TFIIB. Here, the authors use cryo-EM to show how the RNAP from the Vaccinia virus recognizes promoters, identifying transcription factor VITF-3 as an atypical TBP/TFIIB pair.