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The authors identify pre-TCR as a key biomarker and therapeutic target in T-ALL. Targeting it with an anti-pTα antibody–drug conjugate inhibits leukemia-initiating cells and tumor growth in mice, offering promise for relapsed/refractory T-ALL treatment.

Higgins et al. present an AI tool that uses patient data to personalise treatment for Helicobacter pylori, the leading agent of gastric cancer, demonstrating improved eradication rates over prescribed therapies in retrospective clinical analysis.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Ring ATPase translocases that operate on disordered substrates adopt lockwasher architectures and use a hand-over-hand mechanism. By challenging the dsDNA packaging motor of bacteriophage ϕ29 with hybrid and dsRNA, the authors propose that the motor cycles between planar and lock-washer structures.

Genetic diversity in social genes is expected to be shaped by conflict. Here, the authors show that in Dictyostelium discoideum, social genes in fact exhibit diversification patterns consistent with relaxed purifying selection, likely due to their expression only in intermittent social generations.

High-dimensional datasets derived from time-resolved live imaging of leukocytes in mice were used to identify leukocyte identities and dynamic neutrophil states with high cellular resolution.

Zebrafish patient-derived xenograft models (zAvatar) can be used to study cancer biology as well as to predict patient clinical outcomes and response to therapies. Here, in a cohort of 55 patients with colorectal cancer, the authors report that the zAvatar-test can predict response to chemotherapy and clinical outcome with 91% accuracy.

Torrano et al. use bioinformatics analyses to identify PGC1α as a transcriptional regulator of a metabolic program downstream of ERRα that opposes metastatic dissemination in prostate cancer.

The regulation of flowering is best understood in annual plants which flower only once in their lifetime, whereas the repeated cycles of growth and flowering in perennials have not been extensively studied. The identification and study of the perpetual flowering 1 mutant of the perennial Arabis alpina, now gives insight into the different mechanisms of flowering regulation in perennial and annual species, and suggests that patterns of chromatin modification may have a role.

Forest carbon source and sink processes may have contrasting climatic sensitivities. This analysis on 177 coniferous forest sites shows that carbon fluxes and wood formation are coupled but not fully synchronous at intra-annual scales, with peaks in cambial activity preceding those in photosynthesis and respiration.

Here the authors present the low input capture Hi-C (liCHi-C) method, a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. liCHi-C identifies new disease-associated genes and structural variants to ultimately illuminate their pathogenic effects.

Early life exposure to endocrine disrupting chemicals has been linked to increased adiposity during adulthood. Here Chamorro-García et al. show that ancestral exposure to the obesogen tributyltin causes obesity in untreated F4 generation male descendants by inducing heritable changes in genome architecture that promote a thrifty phenotype.

RPSAP52 is an antisense-transcribed pseudogene of HMGA2 that positively regulates HMGA2 expression. Here, the authors show that reexpression of RPSAP52 promotes tumorigenicity by facilitating IGF2BP2 binding to its mRNA targets and consequently regulates the balance of LIN28B and let-7 levels.

Sturm et. al developed a 2 to 4 h antibiotic susceptibility test based on bacterial vibrations. This diagnostic test applies to the most frequently found gram-negative bacteria in bloodstream infections and demonstrates its potential in contributing to faster treatment decisions.

In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings.

Several clinical trials and experimental studies that could have a major impact on the treatment of patients with ischaemic stroke were published in 2012. The studies cover all therapeutic options, including stroke prevention, recanalization and thrombolysis, neuroprotection, and promising new therapeutic approaches focused on neurorepair.

Metastatic dissemination contributes to the lethality in pancreatic ductal adenocarcinoma (PDAC). Here, the authors perform RNA-sequencing on patient derived circulating tumor cells (CTCs) and identify three major CTC subgroups, and show the therapeutic potential of targeting LIN28B/let-7 pathway to halt cancer metastasis.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.

Intrahepatic cholangiocarcinoma is an aggressive cancer of the bile duct with few treatment options and a below 10% five-year survival rate. Here Sia et al. show a novel FGFR2–PPHLN1 fusion and ARAFmutations that may represent future potential therapeutic targets.

Ventricular arrhythmia is a leading cause of death in patients with diabetes. Here the authors show that inflammasome activation and ILK-1β production in cardiac macrophages cause arrhythmia in diabetic mice, which can be successfully treated using agonists to IL-1β receptor or NLRP3 inhibitors.

Highly pathogenic avian influenza (HPAI) A/H5N1 has recently emerged in the Americas and has been implicated in mass die-off events of pelicans and sea lions. Here, the authors report sampling and characterisation of HPAI A/H5N1 genomes from five marine mammal and seabird species in Peru.

Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

Circular RNAs can contribute to tumour progression. Here the authors show that two circular RNAs, circCsnk1g3 and circAnkib1 promote sarcoma growth by controlling the expression of interferon related genes and pro-inflammatory factors in sarcoma cells

An integrated analysis of over 100 single-cell and single-nucleus transcriptomics studies illustrates severe acute respiratory syndrome coronavirus 2 viral entry gene coexpression patterns across different human tissues, and shows association of age, smoking status and sex with viral entry gene expression in respiratory cell populations.

Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.