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In a case series of eight pediatric patients with systemic lupus erythematosus, dermatomyositis or systemic sclerosis, autologous anti-CD19 CAR T cell therapy was feasible, safe and effective in reducing disease activity.

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.

Population-level analyses and in vitro experiments show that a specific genetic variant of cyclin D3 inhibits the growth of the malaria-causing parasite Plasmodium falciparum in erythrocytes, and suggest that its high frequency in Sardinia was driven by past endemic malaria.

The authors show that plasma AT(N) biomarkers can distinguish Alzheimer’s disease and frontotemporal lobar degeneration in diverse Latin American populations. Using machine learning and integrating neuroimaging, significant diagnostic accuracy was achieved, enhancing clinical assessments of these conditions in Latin America.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Da Pra, Boriati and colleagues show that physiological glucocorticoids suppress growth-factor-induced cardiomyocyte regeneration by inhibiting ERK signaling and propose glucocorticoid receptor antagonism as a strategy to enhance their protective and regenerative effects.

A distinctive population with high hunter-gatherer ancestry persisted 3,000 years later than in most European regions, contributing to later Lower Rhine–Meuse Bell Beaker users.

Bohlen and colleagues report that the E3 ubiquitin ligase CBL is necessary for the development, tolerance and activation of B cells in humans, unlike in mice where CBL deficiency results in loss of T cells.

Pseudaminic acids (Pse) are a family of carbohydrates found within bacterial lipopolysaccharides, capsular polysaccharides and glycoproteins. Now, monoclonal antibodies have been developed that recognize diverse Pse across several bacterial species, enabling mapping of the Pse glycoproteome and demonstrating therapeutic potential against multidrug-resistant Acinetobacter baumanii in in vitro and in vivo infection models.

Glucose deprivation triggers the secretion of the cytokine LIF, which promotes angiogenesis and immune suppression in lung cancer models.

Pinci et al. examine the link between genetic variants in the DSG2 gene and arrhythmogenic cardiomyopathy by integrating population, literature, and clinical data. They show that disease risk depends on variant type, location, and multilocus interactions, refining genetic diagnosis and risk assessment.

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Anti-tumor functions of low-avidity T cells are often suboptimal. Here the authors show that genetic disruption of TIGIT in TCR-engineered T cells enhances their anti-tumor activity against pancreatic and other gastrointestinal cancers by increasing TCR signal strength.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

The role of oxytocin in modulating astrocytes during stress behaviour is not fully understood. Here the authors show that in the amygdala, oxytocin modulates stress related behaviour by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium.

By mapping the photocycles of reversibly switching fluorescent proteins, the authors show that tuned activation and red/NIR co-illumination lead to increased signal and reduced photobleaching, prolonging live-cell imaging across super-resolution and multiplexing modalities.

A model trained to generate spatial proteomics profiles and predict the expression of 40 biomarkers directly from histopathology slides is shown to improve survival and treatment response prediction in patients with lung cancer.

Researchers develop a new way to selectively remove ion channel proteins by recruiting the body’s own NEDD4-2 enzyme using custom nanobodies, offering a precise and general strategy for future drug development.

Spinal cord organoids from SMA patients reveal widespread neurodevelopmental defects. Single-cell and functional analyses show global dysregulation, which can be rescued by SMN-increasing therapy, stressing the importance of timely intervention.

Beneficial effects of fasting combined with endocrine therapy for oestrogen receptor-α-expressing breast cancers can be recapitulated using exogenous glucocorticoid receptor ligands instead of fasting to reduce harmful effects.

Asymmetric cell division often requires alignment of the mitotic spindle to cortical polarity cues. Here the authors show that cortical Wnt signaling induces formation of a complex between NuMA/dynein microtubule motors, LRP6 and β-catenin that promotes asymmetric division.

Klose and colleagues show that the neuropeptide vasoactive intestinal peptide (VIP) acts on LGR5⁺ epithelial stem cells in the gut to restrain their proliferation and differentiation to secretory cell types. This VIP–VIPR1 interaction acts to limit type 2 immune responses.

To function safely and effectively, medical AI models must adapt automatically to differences in users, health systems, geographies, diseases and populations. This Perspective proposes context switching as the defining paradigm of medical AI, outlining early strategies and opportunities for development.

How neural responses to boundaries develop in the subiculum remains unknown. Here authors show that the receptive fields of Boundary Vector Cells (neurons signalling vector displacement to boundaries) are altered by environment geometry, with directional tunings aligning with square arena walls, including during development.

CNS toxicity was unexpectedly observed for anti-miR-17 RGLS4326 in nonclinical studies. Here, authors identify AMPA receptor inhibition as the likely culprit. Replacement of 3’-terminus guanine to adenine leads to discovery of farabursen (RGLS8429) that is devoid of CNS toxicity.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Supersolids combine superfluid and crystal order and their response to external driving remains unclear. Now it is shown that, in a dipolar supersolid, rotation induces synchronization of the crystal motion via vortex nucleation.

In this work, authors show that via CD48–Als6 interaction, eosinophils can kill Candida albicans in vitro and protect against systemic candidiasis in vivo, reducing the fungal growth and improving survival of mice.

Synthetic fibril strain 1B is a pathogen that is capable of self-replication and inducing glial cytoplasmic inclusions in vivo in mice, and the structural features of 1B may underlie the pathology of individuals with multiple-system atrophy.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

Forming self-assembled soft materials with unconventional properties can be useful in many different applications. Here, Sciortino and co-workers have designed and experimentally realized a one-pot DNA hydrogel that melts both on heating and on cooling.

Vanni et al. show a role for microtubules in YAP/TAZ mechanosignalling. Mechanoresponsive microtubule reorganization into centrosomal arrays allows for AMOT delivery to pericentrosomal proteasomes and degradation, leading to YAP/TAZ activation.

A wireless ingestible sensor that is equipped with an oxidation–reduction potential sensor, electrochemical reference electrode, and pH and temperature sensors can be used to measure redox balance along the human gut.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

tRNA modifications are essential for function, yet their timing relative to processing is unclear. Here, the authors show that queuosine and derivative modifications occur before splicing of pre-tRNA^Tyr, with cryo-EM confirming direct recognition by the QTRT1/2 complex.

Li, Burgos-Bravo and colleagues report that NDF phase separation regulates FACT condensation, which enhances transcription by generating a localized biochemical environment that promotes nucleosome disassembly while preserving chromatin integrity by retaining histones.

Researchers developed a self-driving lab, including automated confocal imaging, that uses machine learning to rapidly map the phase behavior of biomolecular condensates.

High-affinity ligands were developed that specifically bind aggregated TDP-43, are selective over common co-pathologies, and possess pharmacokinetic profiles suitable for PET imaging to visualize TDP-43 pathology in the brains of patients.

Prostate cancer (PCa) evaluation remains challenging due to its heterogenous and multifocal nature. Here, the authors reconstruct the nuclear chromatin compartmentalization of PCa patients-derived biopsies distinguishing two epigenetic subtypes and deriving an 18-gene signature with prognostic value on TCGA samples that is further validated with multiple independent PCa cohorts.

Single cell profiling of tissue from patients undergoing therapy has the potential to identify drug-induced immune changes. Here the authors show a skin scRNA-seq study of psoriasis patients treated with an IL-23 inhibitor and characterize changes in cell states during early treatment.

It has been argued that air temperatures over mountain glaciers are decoupled from surrounding warming, which could slow down melting. Here the authors show that this effect will weaken with future glacier retreat, leading to a recoupling of temperatures from the 2030s onwards.

Pianca and Sacchi et al. unveil an important role for glucocorticoids and their receptor (GR) in cardiomyocyte cytoarchitectural/metabolic maturation, cell cycle exit and loss of regenerative ability, and they propose GR antagonization as a strategy for heart regeneration.

Water vibrational motion, which occurs on the few-femtosecond timescale and underpins energy transfer within the hydrogen bonding network, has remained challenging to observe in real time due to constraints in time resolution. Here, the authors investigate the ground state vibrational dynamics of liquid water using a sub-5 fs near-infrared pump pulse and few-fs ultraviolet probe pulses, observing rapid dephasing of the OH stretch mode that precedes its relaxation via coupling to the bend modes.

In the final analysis of a phase 1/phase 2 trial of autologous GD2-targeting CAR T cells in pediatric patients with high-risk metastatic, relapsed or refractory neuroblastoma, treatment was overall well tolerated, with an objective response rate of 66%. These findings were further supported by a case series involving the same therapy in a similar patient population.