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Neoadjuvant immunochemotherapy against NSCLC has been tested in clinical trials. Here, the authors follow up longer-term survival and measure immune cell phenotype changes in a single-arm phase II clinical trial of neoadjuvant immunochemotherapy, indicating association of intratumoural TCR diversity and CD8 T cell positioning.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

Here, the authors show that physiological alpha-synuclein supports mitochondrial ATP homeostasis via interactions with ATP synthase and AK2, whereas its disease-linked mutants, truncated forms, and aggregates lose these interactions.

Ludewig and colleagues show that adenovirus immunization fosters the formation of pulmonary immune-stimulating niches underpinned by fibroblastic stromal cells that maintain ‘inflating’ memory CD8⁺ T cells through the provision of interleukin-33.

Despite their differences, the rarer sarcoma CIC::DUX4 sarcoma (CDS) is typically treated with therapies developed for Ewing Sarcoma (EwS) with limited success. Here, the authors develop a co-clinical drug response profiling platform to establish patient-derived CDS and EwS tumoroids, identifying MCL1 inhibition as a promising therapeutic approach in CDS.

Literature produced inconsistent findings regarding the links between extreme weather events and climate policy support across regions, populations and events. This global study offers a holistic assessment of these relationships and highlights the role of subjective attribution.

The biological role of 2′-O-methylation of host and viral mRNA has remained elusive. Thiel and co-workers show that this modification modulates the induction of type I interferon and sensitivity to interferon.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Digestive surgical leaks manifesting days after a successful surgery can lead to severe complications and affect healthcare worldwide. Here, the authors address the problem holistically with a hydrogel patch capable of sealing tissues, while detecting imminent leaks via a smartphone-operated ultrasound probe.

The authors present experimental evidence of three-dimensional superinsulation in a nanopatterned slab of NbTiN. In the electric Meissner state, they find polar nematic order arising from ferroelectric alignment of short electric strings excited by external electromagnetic fields.

Genetic variation in the IFNλ locus has been associated with clearance of hepatitis C virus. Here, the authors show that a single amino-acid variant of IFNλ4 affects its antiviral activity and that patients carrying the impaired variant have better viral clearance rates.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

The RNA editing enzyme ADAR1 blocks interferon responses triggered by cytosolic RNA sensors, and has been proposed as a potential target in immuno-oncology. Here, the authors report that BRCA1/2 and ADAR1 are synthetic lethal, showing that ADAR1 depletion in BRCA1-mutant cells causes autocrine interferon poisoning

A single-cell ex vivo screening of repurposable drugs in glioblastoma and machine learning of drug–target networks show that anti-tumor neuroactive drugs converge on the AP-1/BTG pathway, based on which prediction models and experimental in vivo and in silico validation identify the anti-depressant vortioxetine as a potential therapeutic agent.

Neurotoxicity impacting the central and peripheral nervous systems is a considerable adverse effect of both conventional and novel cancer therapies. In this Review, Karschnia et al. outline what is currently known about the mechanisms that underlie the clinical symptoms of central nervous system injury and peripheral neuropathy and the ongoing development of interventions to treat and prevent this unmet medical need.

Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.

Broadly neutralizing antibodies (bnAbs) develop in a minority of HIV-infected individuals. Analyzing data from more than 4,000 infected individuals, Alexandra Trkola and colleagues identify viral, host and disease factors associated with the development of bNAbs that may inform future vaccine design.

Roesch and colleagues use clinical datasets and mouse models of BRAF-mutant melanoma to reveal a role for IL-17A in positive responses to anti-PD-1 and anti-CTLA-4 therapy, which they also link to infiltrating neutrophils.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Medulloblastoma in children is a difficult cancer to treat and the immune response to this tumour is not fully understood. Here the authors characterise and validate T cell epitopes from these cancers using an immunopeptidomics approach, comparing different molecular subtypes.

Here, Bachmann et al. provide data on long-term dynamics of the HIV-1 reservoir in 1,057 individuals on suppressive antiretroviral therapy and show that in 26.6% of individuals the reservoir increases. Viral blips and low-level viremia are significantly associated with a slower reservoir decay.

ALS is somewhat heritable, but the genetic basis is not completely understood. Here, the authors identify alterations in splicing in neurons associated with amyotrophic lateral sclerosis and uncover several associated genetic loci, with a potential link to nuclear pore defects.

Businesses increasingly experiment with monetary impact valuation to assess their sustainability impacts, raising both promise and concern. We propose a scientific approach — grounded in eight principles — to ensure valuation serves sustainability rather than distorts it.

Heat pumps are essential for sustainable heating, but their performance varies widely. Here, authors analyze data from 1023 systems, revealing that 17% of air-source and 2% of ground-source heat pumps operate below efficiency standards. Additionally, 11% are improperly sized, highlighting the need for optimization.

Growing up in the rich microbial environment of a farm strongly influences the maturation of the gut microbiome in the first year of life, which helps protect against the development of asthma in children.

Anthropogenic contaminants enter sea ice, with varied behavior depending on size (dissolved, colloidal, particulate) and particle density—providing insights into poorly understood incorporation mechanisms.

Functional profiling of enzyme family classes is essential for clinical tissue phenotyping. Here, the authors develop and apply an alternative approach in activity-based protein profiling of serine hydrolases, revealing molecular layers of catalytic enzyme fractions involved in palmitate remodeling and lung adenocarcinoma progression.

The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.

Defect tolerance is important in order to ensure the mechanical integrity of synthetic materials and biological tissues. Here the authors demonstrate that toughening mechanisms provide soft collagenous tissues with high defect tolerance, with important implications for biomedical applications.

Reversible palmitoylation regulates the activity and localisation of numerous proteins. Here, Kuo et al develop nanobody-based reagents to specifically target palmitoylation of individual proteins, using this approach to tune the biophysical properties of a single ion channel to prevent arrhythmias in cardiac myocytes.

A disturbed microbial network characterizes relapsing refractory Crohn’s disease and antedates disease recurrence after surgical removal of the active disease segment.

Individuals seeking post-exposure prophylaxis (PEP) for HIV may represent an important risk group for future HIV infection. Here the authors find HIV infections at long-term follow-up in 22 of 348 men who have sex with men, and 0 of 623 other PEP seekers.

Peyer’s patches (PPs) are sites of antibody production in the gut mucosa. Carroll and colleagues show the mechanosensory channel protein Piezo1 is required for the homeostatic maintenance of PPs. Specific loss of Piezo1 in FRCs disrupt PP structure and function, resulting in reduction of fecal IgA production and gut immunity.

Cancers in different populations have been shown to be genetically distinct. Here, the authors sequence breast cancers from Mexican-Hispanic patients and find that these patients have a higher percentage of Akt1 mutations compared to Caucasian and Asian populations, suggesting these are clinically actionable.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Protein level information enables the identification of potential biomarkers and therapeutic targets for breast cancer. Here, the authors perform proteomic analysis of 2 cohorts of breast cancer surgical specimens and identify distinct subtypes, immune features and survival outcomes.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The V3-crown of the HIV-1 envelope protein largely elicits non-neutralizing antibodies. Here, the authors show that the V3-crown can be targeted by broadly neutralizing designed ankyrin repeat proteins recognizing two conformations one of which resembles CCR5- bound V3.

Recently triggered seismic events such as the Pohang earthquake have exceeded predictions of average energy releases by a factor of 1000. A new framework is proposed to define maximum event magnitudes as a function of pre-existing critical stresses and fluid injection volume.

The classification of breast lesions as indolent or aggressive to tailor treatment is crucial. Here, the authors use single-cell transcriptomics and multiparametric imaging of a breast cancer mouse model, report distinct tumor-immune features for the two types of lesions, and suggest the role of IL-17 signaling in disease progression.

The interplay of migration and adaptation was key in shaping species’ responses to Quaternary climate change. Illustrating this, Luqman et al. show that adaptive responses in a plant species emerged from climate-induced range shifts due to heterogenous sieving of adaptive alleles across space and time.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.