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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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Here the authors show that CD4⁺ effector T cells prevent or reverse CD8⁺ T cell dysfunction by licensing Kupffer cells to trigger IL-27 production, defining a liver-specific immune circuit and a potential target for chronic HBV therapeutics.

Dengue and chikungunya are an increasing public health concern in Europe, and Italy is particularly affected. Here, the authors analyse travel-related cases and outbreaks in Italy from 2006 to 2023 and assess current transmission risks.

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 circuit mechanisms underlying emotion recognition are unclear. Here, Dautan et al. show a role for a long-range feedback loop comprising somatostatin inhibitory projections from the medial prefrontal cortex (mPFC) to the retrosplenial cortex (RSC) and excitatory feedback projections from the RSC to the mPFC.

Loss-of-function variants in thyroid hormone transporter MCT8 cause a neurodevelopmental and metabolic disorder. Here the authors identify genotype-phenotype relationships, advance insights in MCT8 (dys)function and create a pathogenicity-severity variant classifier.

A photonic experiment demonstrates protective measurements, a type of weak measurements. These make it possible to determine the expectation value of the polarization of a photon from a single measurement.

Tissue fluidification in invasive breast carcinoma is accompanied by mechanical stresses that compromise nuclear integrity and liberate DNA, resulting in the activation of a pro-inflammatory response that shape tumour evolution and progression.

NK cells play an important role in anti-tumour immunity, however, the immune-hostile microenvironment often impairs their function. Here authors show that cancers disable autophagy in NK cells, and by restoring this process, intra-tumour NK cells could be re-invigorated.

Single-cell and spatial gene expression analyses of pancreatic ductal adenocarcinoma uncover a population of interleukin-1β-expressing macrophages that drive inflammatory reprogramming of neighboring tumour cells leading to disease progression and poor prognosis for patients.

Fifteen years’ follow-up of clinical development and real-world data from 43 patients show that gammaretroviral gene therapy for adenosine deaminase deficiency has a positive long-term efficacy profile, warranting continued safety monitoring of patients receiving gene therapy.

Here the authors show that the DNA helicase WRN ‘s interaction with the single stranded DNA binding protein RPA is regulated through specific phosphorylation by Casein Kinase 2. This regulation is critical for resolving DNA replication stress caused by G-quadruplexes.

Human primary and metastatic tumors harbor CD4⁺ T_reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T_reg-like CD4⁺ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES⁺ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.

SETBP1 variants occur as somatic mutations in several malignancies and as de novo germline mutations in developmental disorders. Here the authors provide evidence that SETBP1 binds to gDNA in AT-rich promoter regions to promote target gene upregulation, indicating SETBP1 functions directly to regulate transcription.

Macrophages can promote tumorigenesis and enhance the antitumour response. This Review discusses the molecular mechanisms underlying the reprogramming of macrophages in the tumour microenvironment and provides an overview of macrophage-targeted therapies for the treatment of cancer.

This paper identifies the top-50 priority questions for meiofaunal research, highlighting their critical roles in biogeochemical cycles and biodiversity. It calls for a balanced research agenda, international cooperation, and advances in technology to overcome current challenges and unlock meiofauna’s full potential.

Employing a candidate gene approach, Mancina et al. identify a genetic variant of the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene that reduces susceptibility to fatty liver disease. Functional studies in vitro and in vivo demonstrate that targeting PSD3 protects against fatty liver disease.

Cassatella and colleagues identify CD66b⁻CD64^dimCD115⁻ cells in the human bone marrow as the earliest neutrophil-committed progenitor cells described to date.

West Nile virus is an animal pathogen that has spread rapidly in Europe in recent years, causing several human deaths. This study investigates the spatial and temporal dynamics of the virus circulation between Africa (its place of origin) and Europe.

Here the authors use three different mouse models to show that prior infection or mRNA vaccination can protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) independently of antibodies, highlighting the importance of T cell-derived interferon-γ (IFN-γ) in host defense and the need to consider this measure of protection in vaccination.

Precision oncology relies on model systems that reflect the genomic heterogeneity of human cancers. Here the authors characterize a panel of 151 colorectal cancer cell lines with respect to genetic mutations, expression profiles and drug sensitivity to identify new therapeutic targets.

Maltese et al. show in mice that experiencing an adverse event affects future interaction with others experiencing the same stressor. These self-experience socioemotional reactions are orchestrated by the corticotropin-releasing factor system in the medial prefrontal cortex.

A modified fluctuation test applied to colorectal cancer cells shows that EGFR/BRAF inhibitor-induced persisters slowly proliferate and have an increased mutation rate. Error-prone DNA polymerases are identified as potential targets to avoid tumor recurrence following treatment with these drugs.

Non-canonical transcripts containing LINE1 transposable elements maintain naive CD4⁺ T cell quiescence and interfere with gene expression in cis. LINE1-containing transcripts are downregulated upon T cell activation.

A common genetic cause of Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is expansion of the intronic hexanucleotide repeat (GGGGCC)_n in C9orf72. Here the authors reveal that the RNA (GGGGCC)_n expansion repeat associated with ALS/FTD can generate condensates in the absence of proteins, highlighting the potential relevance of targeting RNA-structures to treat neurodegenerative diseases.

The role of epigenetic deregulation in colorectal cancer (CRC) is not fully understood yet. Here the authors use patient-derived organoids, epigenomics and single-cell RNA-seq to reveal that YAP/TAZ are key regulators that bind to active enhancers in CRC and promote tumour survival.

Leukaemia development has been reported as an associated risk of haematopoietic stem cell gene therapy (HSPC-GT) using retroviral vectors in different diseases. Here, the authors show a case of T-cell acute lymphoid leukaemia in a patient with Adenosine Deaminase-deficient Severe Combined Immunodeficiency (ADA-SCID) treated with retroviral gene therapy.

slanDCs represent a population of dendritic cells whose role in cancer immune surveillance is not known. Here, the authors reveal that in cancer patients, slanDCs accumulate in the metastatic tumour-draining lymph nodes but not primary carcinoma sites, suggesting their involvement in nodal immune responses to cancer cells.