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JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms

1 day ago
Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O(2)), we sought to determine whether the modality of HIF-1 activation directs its function. Through...
David Kealy

Digital Health Tools Embedded in a Cancer Genetics Clinic: Observational Study

1 day ago
CONCLUSIONS: DHTs are feasible and can capture clinically meaningful psychological and physiological data in high-risk pediatric and family populations with LFS. They enable timely detection of distress and facilitate targeted interventions. Our findings can inform best practices for patient-centered DHT integration into clinical care, with relevance to pediatric oncology and broader digital health contexts.
Sujay Nagaraj

Discovery of pyrrolopyrimidinone inhibitors of the BCL6-SMRT corepressor interaction

2 days ago
B-cell lymphoma 6 (BCL6) is a transcriptional repressor protein central to the development and maintenance of germinal centers (GCs) during the humoral immune response. BCL6 is often deregulated in diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin's lymphoma, and inhibition of the protein-protein interaction between BCL6 and corepressors has been implicated as a therapeutic strategy. Based on a previously identified small molecule binding site on the BCL6 BTB domain, we carried out a...
Iain D G Watson

B cells drive CD4 T cell immunosenescence and age-associated health decline

4 days ago
Dysregulation of the adaptive immune system is a key feature of aging and is associated with age-related chronic diseases and mortality. Here, we find that T cell aging, especially in the CD4 subset, is controlled by B cells. B cells contributed to the age-related reduction of naive CD4 T cells, their differentiation toward immunosenescent T cell subsets, and age-associated T cell receptor clonal restriction. Concurrently, mice lacking B cells displayed improvements in health span and life span....
Saad Khan

Non-invasive screening in hereditary cancer: a randomized controlled trial to test cell-free DNA-based early detection in the CHARM consortium

5 days ago
Individuals with hereditary cancer syndromes are born with germline genetic variants that significantly increase their lifetime risk of developing multiple cancers. Cancer rates and overall mortality can be reduced with intensive surveillance to facilitate early cancer detection. However, participating in diagnostic imaging and endoscopy surveillance programs is often time-consuming, overwhelming, inconvenient, and anxiety-inducing. To improve this, multi-cancer early detection tests are being...
Kirsten M Farncombe

IUGC: A benchmark of landmark detection in end-to-end intrapartum ultrasound biometry

6 days ago
Accurate intrapartum biometry plays a crucial role in monitoring labor progression and preventing complications. However, its clinical application is limited by challenges such as the difficulty in identifying anatomical landmarks and the variability introduced by operator dependency. To overcome these challenges, the Intrapartum Ultrasound Grand Challenge (IUGC) 2025, in collaboration with the International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), was...
Jieyun Bai

Tutorial: annotation of animal genomes

6 days ago
As DNA sequencing technologies improve, it is becoming easier to sequence and assemble new genomes from non-model organisms. However, before a newly assembled genome sequence can be used as a reference, it must be annotated with genes and other features. This can be conducted by individual laboratories using publicly available software. Modern genome annotations integrate gene predictions from the assembled DNA sequence with gene homology information from other high-quality reference genomes and...
Zoe A Clarke

Characteristics and Outcomes of Adults Hospitalized With Childhood-Onset Complex Chronic Conditions

6 days ago
CONCLUSIONS AND RELEVANCE: In this cohort study, young adults with 4Cs had longer acute care medical hospitalizations, accounting for 10.7% of all young adult hospital bed-days, and more rehospitalizations than other young adults. The results suggest that this population should be prioritized for targeted measures to reduce inpatient stays and improve care. The Charlson Comorbidity Index may be of limited utility for capturing comorbidities in this population.
Sarah L Malecki

<em>Streptococcus</em><em>dysgalactiae</em> subsp. <em>equisimilis</em> from Diseased Pigs Are Genetically Distinct from Human Strains and Associated with Multidrug Resistance

6 days ago
Streptococcus dysgalactiae subsp. equisimilis (SDSE) has historically been recognized as a human pathogen, yet β-hemolytic streptococci consistent with SDSE have been documented in pigs for nearly a century. To investigate the population structure of porcine SDSE and the phylogenetic relationships between swine and human strains, we characterized 41 isolates recovered from diseased pigs in Quebec, Canada (2019-2022). Infected animals spanned all major production stages and frequently presented...
Fengyang Hsu

Longitudinal Interaction Between Individualized Gut Microbial Dynamics and Diet Is Associated with Metabolic Health in School-Aged Children

6 days ago
CONCLUSIONS: These findings suggested that the variation in the gut microbiota dynamics could be considered as a possible complementary biomarker to understand the individualized responses within dietary interventions aimed at improving metabolic health in childhood. Further well-designed intervention study is needed to define these observational associations.
Changcan Feng

Membrane and Proteome Allocation Constraints in Escherichia coli Models during Overflow Metabolism

1 week 2 days ago
The allocation of finite cellular resources is a fundamental principle that dictates microbial metabolic strategies and gives rise to complex phenomena, such as overflow metabolism, characterized by the production of respiro-fermentative byproducts, including acetate, during rapid growth. While proteome-constrained models have successfully predicted overflow metabolism in Escherichia coli, they often overlook the distinct biophysical and energetic costs associated with protein localization. The...
Mauricio Garcia-Benitez

Glioblastoma stem cells show transcriptionally correlated spatial organization

1 week 4 days ago
Glioblastoma (GBM) is an aggressive brain cancer with a poor survival rate. Despite hundreds of clinical trials, there is no effective targeted therapy. Glioblastoma stem cells (GSCs) are an important GBM model system. In culture, these cells form spatial structures that share morphological aspects with their source tumors. We collected 17,000 phase-contrast images of 15 patient-derived GSC lines growing to confluence. We find that GSCs grow in characteristic multicellular patterns depending on...
Shamini Ayyadhury

Organic chemicals of Arctic concern in Russian coastal seas

1 week 5 days ago
Arctic ecosystems face significant threats from chemicals of global concern. Persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) have been consistently detected in the Arctic through decades of monitoring. POPs are known to bioaccumulate in food webs, and both POPs and PAHs are toxic posing risks to wildlife and human health. While regular monitoring activities have been implemented in most Arctic countries, information from the Russian Arctic is still limited. This...
Xi-Ze Min

Disseminated pediatric low-grade glioma and hydrocephalus: a multinational consortium analysis of incidence and mortality

1 week 5 days ago
CONCLUSIONS: This study represents the largest and most comprehensive cohort of patients with DPLGG to date. While histopathology and tumor location were associated with hydrocephalus in this cohort, the dissemination pattern was not directly associated with hydrocephalus incidence but rather the timing of hydrocephalus diagnosis. Hydrocephalus does not impact survival in patients with DPLGG; however, it is associated with worse functional outcomes.
Alexander T Lyons

Proteins in the Genome Browser: integration of phylogenies, alignments, and structures with nucleotide-level evidence in JBrowse 2

1 week 6 days ago
Recent advances in protein structure prediction have created high-confidence candidate structures for every protein-coding gene in a genome. Concomitantly, many software packages have been created to visualize protein multiple sequence alignments (MSAs), protein structures, and protein annotations. However, few software tools can highlight the direct relationship between nucleotide variation of protein-coding genes in genome space and the evolutionary and structural context of that variation in...
Colin Diesh

CACHE Challenge #3: Targeting the Nsp3 Macrodomain of SARS-CoV-2

1 week 6 days ago
The third Critical Assessment of Computational Hit-finding Experiments (CACHE) challenged computational teams to identify chemically novel ligands targeting the macrodomain 1 of SARS-CoV-2 Nsp3, a promising coronavirus drug target. Twenty-three groups deployed diverse design strategies to collectively select 1739 ligand candidates. While over 85% of the designed molecules were chemically novel, the best experimentally confirmed hits were structurally similar to previously published compounds....
Oleksandra Herasymenko

SorghumBase: a knowledgebase for sorghum genomics, phenomics, and stakeholder engagement

2 weeks 1 day ago
Centralizing valuable community data and resources into a user-friendly interface and accessible repository has become essential for agricultural science; embracing Findable Accessible, Interoperable, and Reusable (FAIR) principles is now standard for effective databases. SorghumBase (https://www.sorghumbase.org) is a knowledgebase designed for the sorghum research community. The SorghumBase team curates genomic, transcriptomic, variation, and phenotypic information and aggregates community...
Nicholas Gladman
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