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The International Cancer Genome Consortium Accelerating Research in Genomic Oncology (ICGC ARGO) project is an international initiative to sequence germline and tumour genomes from 100,000 cancer patients across 13 countries and 22 tumour types. By integrating genomic data with comprehensive clinical information including treatment outcomes, lifestyle, environmental exposures and family history, ICGC ARGO aims to accelerate the application of genomic insights in cancer diagnosis, treatment and...

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While hospital readmission is the most common health system performance metric after transcatheter cardiac interventions, emergency department (ED) visits are rarely evaluated. We aimed to synthesize the incidence, causes, predictors, costs, and outcomes of ED visits following transcatheter procedures in patients undergoing percutaneous coronary interventions (PCI), atrial septal defect (ASD) closures, patent foramen ovale (PFO) closures, and transcatheter aortic valve interventions (TAVI)....

CONCLUSIONS: D1 and D2 represent distinct neurobiological mechanisms underlying MDD. The validation in a general population-based cohort and in a cohort sample with depressive symptoms delineates mechanisms underlying heterogeneity in MDD.

BackgroundApproximately one-third of adults with major depressive disorder (MDD) experience limited response or intolerable side effects with existing pharmacotherapies. As such, innovative treatments targeting novel biological pathways are under investigation. One promising area of research is the gut microbiome and its influence on mood through the microbiota-gut-brain axis. Clinical studies have begun evaluating microbiome-targeted interventions such as probiotics, prebiotics, synbiotics, and...

CONCLUSIONS: Immunotherapy in PSC-associated BTCs appeared safe, with a potential signal of effectiveness. Given the sample size and retrospective design, these results are hypothesis-generating. Together, these results demonstrate the unique biology underlying PSC-associated BTCs, highlighting the need for prospective trials and the development of specialized treatment strategies.

The Reactome Knowledgebase (https://reactome.org) is a freely accessible, expert-curated, open-source, and open-data resource that describes human biology in molecular detail. It spans normal physiology as well as disease mechanisms, including the impact of genetic variation and drug action. Reactome content is continuously expanded and revised, with automated workflows now monitoring retracted publications to maintain data integrity. To meet the needs of a growing user base, Reactome has...

Pediatric Low-Grade Glioma (pLGG) is the most common pediatric brain tumor, and radiomics-based machine learning (ML) models have shown promise in identifying BRAF fusion and BRAF p.V600E mutation. This bicentric retrospective study included 495 children diagnosed between 1999 and 2023. The local hospital dataset comprised Magnetic Resonance Imaging (MRI) scans of patients with BRAF fusion (n = 190), BRAF p.V600E mutation (n = 95), FGFR1 (n = 25), and other molecular subtypes (n = 144), while an...

Acute respiratory distress syndrome (ARDS) is a major cause of mortality in severe viral pneumonia, including COVID-19. Current antivirals reduce viral replication bu fail to address the dysregulated host inflammation that drives lung failure, while unmodified mesenchymal stromal cells (MSCs) have shown only modest benefits in clinical trials. To overcome these limitations, we engineered MSCs expressoing human ACE2 (MSC^(ACE2)), designed to couple direct antiviral activity with immonoregulation....

Diffuse Large B-Cell Lymphoma (DLBCL) is one of the most aggressive forms of lymphoid malignancies. About 40 % of patients eventually relapse and succumb to the disease within 5 years after diagnosis, underscoring the need for new treatment modalities. B-Cell Lymphoma 6 protein (BCL6) is a repressive transcription factor that is dysregulated in about 40 % of DLBCLs. As a rationale for pursuing BCL6 as a drug target, disrupting complexes between this protein and its co-repressors is thought to...

Acute myeloid leukemia (AML) patients have a poor five-year survival rate highlighting the need for the identification of new approaches to target this disease. AML is highly dependent on glutathione (GSH) metabolism for survival. While the metabolic role of GSH is well-characterized in AML, the contribution of protein glutathionylation-a reversible modification that protects protein thiols from oxidative damage-remains largely unexplored. Therefore, we sought to elucidate the role of protein...

The Arctic, though remote, is exceptionally vulnerable to chemical contaminants that threaten its fragile ecosystems. Bisphenols (BPs), a class of endocrine-disrupting chemicals used in plastics and resins, are now detected across the Arctic, but the risks posed by their many analogues are poorly understood. Most studies have focused on documenting their presence, leaving a critical gap in our understanding of whether these compounds bioaccumulate in Arctic food webs and to what extent local,...

Background: Breast cancer polygenic risk scores (PRS) and traditional risk models (e.g., the Gail model [Gail]) are known to contribute largely independent information, but it is unclear how the overlap varies by ancestry, age, disease type (invasive breast cancer, DCIS), and risk threshold. Methods: In a retrospective case-control study, we evaluated risk prediction performance in 180,398 women (161,849 of European ancestry; 18,549 of Asian ancestry). Odds ratios (ORs) from logistic regression...

CONCLUSIONS: There was no evidence of an association between prenatal fluoride exposure and autistic behaviors in preschool-aged children, in contrast to previous MIREC research findings on lead and phthalates. Given that this cohort has relatively few children with high SRS-2 scores, further research is needed in other groups of children to more fully explore this association.

The biological function of a protein is often determined by its distinct functional units, such as folded domains and intrinsically disordered regions. Identifying and categorizing these protein segments from sequence has been a major focus in computational biology which has enabled the automatic annotation of folded protein domains. Here we show that embeddings from the unsupervised protein language model ProtT5 can be used to identify and categorize protein segments without relying on...

Somatic mutations inactivating TET2 are among the most common drivers of clonal hematopoiesis (CH). TET2 inactivation is associated with monocyte-derived inflammation and improved chimeric antigen receptor T cell function, suggesting it might also impact immunotherapy response. Here, we found that hematopoietic Tet2 mutation in mouse models enhanced the immune checkpoint blockade (ICB) response, which required the combined presence of phagocytes, CD4+, and CD8+ T cells. The effect was lost with...

CONCLUSIONS: Our study highlights gaps in current evaluations of virtual care. Work is needed to improve the quality and standardization of virtual care evaluation to ensure reproducibility, generalizability and comparability of findings. Additionally, better compliance with existing measure definitions and conventions should extend to virtual care. Finally, additional theoretical work is needed to standardize and conceptually frame future virtual care evaluations. Future studies should include...

Decidualization, a highly programmed differentiation process of the uterine stroma, is characterized by significant biochemical remodeling and is essential for pregnancy. However, the functions and molecular mechanisms of lipid metabolism during decidualization remain poorly understood. In this study, a dynamic process of lipid droplet synthesis and degradation is observed during decidual progression, and GSK3 is identified as a potential regulator for lipolysis. Specifically, lipolysis is...

CONCLUSIONS: Heterogeneity in circulating immune cell profiles is associated with PsA clinical features and therapeutic response. The results underscore the potential of immune cell phenotyping to improve prognosis in PsA, which could inform personalised treatment strategies.

A sequence motif representing the DNA-binding specificity of a transcription factor (TF) is commonly modelled with a positional weight matrix (PWM). Focusing on understudied human TFs, we processed results of 4,237 experiments for 394 TFs, assayed using five different experimental platforms. By human curation, we approved a subset of experiments that yielded consistent motifs across platforms and replicates, and evaluated quantitatively the cross-platform performance of PWMs obtained with ten...