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To define and systematically characterize the human E3 ubiquitin ligase (E3) landscape, we generated the E3-ome, a compendium of E3s encoded by the human genome. The E3-ome integrates experimental data, bioinformatics, and published research, revealing 672 high-confidence E3s. We standardized E3 classifications to create a unified framework for annotation and comparative analysis. The E3-ome identified several previously unrecognized domains, motifs, E3 candidates, and relationships, expanding...

Artificial intelligence (AI) has the potential to transform health care; however, successful integration of AI into health care requires overcoming obstacles, such as biases in data and AI models, and addressing challenges in generating sufficient clinical evidence for deployment. In this Viewpoint, we present a community-based, actionable framework for responsible and ethical development, deployment, and integration of AI-based solutions in health care, emphasising bias mitigation and clinical...

CONCLUSION: Our findings demonstrate that inhibiting the TAMs-induced IGF1/PI3K/Zic1 signaling axis results in MB regression and chemosensitization. These results underscore the therapeutic potential of combining clinical CSF1R inhibitor with standard chemotherapy as an effective treatment strategy for SHH MB.

Metagenomes of lignocellulose-degrading microbial communities are reservoirs of carbohydrate-active enzymes relevant to biomass processing. Whereas several metagenomes of natural digestive systems have been sequenced, the current study analyses metagenomes originating from an industrial anaerobic digester that processes effluent from a cellulose pulp mill. Both 16S ribosomal DNA and metagenome sequences were obtained following anaerobic cultivation of the digester inoculum on cellulose and...

Müller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene Plagl1 as a key transcriptional regulator of gliogenesis in the murine retina. Plagl1 is expressed during the RPC-to-glia transition and is dynamically regulated in Müller glia following injury. To define its developmental role, we analyzed Plagl1⁺/⁻pat null mutant retinas at postnatal day 7 (P7), when central retinal...

Clostridium kluyveri is a promising biocatalyst for producing medium-chain carboxylic acids (MCCAs) from waste-derived carbon via chain elongation. MCCAs are platform chemicals with diverse applications across agriculture, food, cosmetics, and fuels and could support tandem resource recovery and sustainable chemical production. However, host defense systems have hindered efforts to engineer C. kluyveri for improved product yields, control over chain length and selectivity, and production of...

CONCLUSIONS: In analyses of biomarkers and composite subtypes for prognosis studies such as in breast cancer, the use of compatible imputation models and penalization methods is recommended for MC modeling in samples with low event numbers and/or with covariate imbalance.

Breast cancer brain metastasis (BCBM) is a devastating disease with limited treatment options, largely due to the presence of the blood-brain barrier (BBB) in the central nervous system (CNS), and thus, the development of effective alternative therapies for BCBM remains a significant unmet clinical challenge. Herein, we found that monocytes, M2 macrophages, and adrenomedullin (AM) were abundantly present in human BCBM. Therefore, we innovatively proposed monocytes/macrophages as promising...

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a Cytosine-Adenosine-Guanine (CAG) repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage...

BACKGROUND: Although severe maternal morbidity (SMM), such as severe hemorrhage and sepsis, can occur from conception to 6 weeks postpartum, most surveillance studies in Canada are restricted to intrapartum cases, with rates approximating 17 per 1000 births. We aimed to characterize the frequency of SMM from conception to 6 weeks postpartum and describe its associations with maternal and clinical characteristics.

CONCLUSION: MRI-based machine learning models may support noninvasive prediction of BRAF mutation status in pLGG. FLAIR is the best-predicting single sequence, but multisequence integration was associated with improved and more balanced performance. These findings support multisequence radiomics as a promising tool to guide precision treatment in pLGG, particularly when tissue sampling is not feasible.

CONCLUSIONS: This pooled analysis provides limited evidence of an association between occupational exposure to chlorinated solvents and lung cancer, though exposure-response trends were noted among exposed individuals.

Despite promising data showing that circulating tumour DNA (ctDNA) dynamics during treatment can inform real-time tumour response and recurrence risk¹, how best to translate these insights into actionable clinical decision-making remains unclear. Here we report results from the EP-STAR trial-a multi-centre, ctDNA-driven, risk-adapted, non-randomized phase II study ( NCT04072107 ; ClinicalTrials.gov) testing whether a risk-adaptive treatment (RAT) strategy guided by on-treatment ctDNA dynamics...

CONCLUSIONS: By integrating multidimensional data, our framework enables the tailored prognostication and clinical decision to meet the multidimensional requirements of research and medicine.

Medulloblastoma (MB) is a biologically and clinically heterogeneous pediatric brain tumor. However, large-scale molecular subgrouping studies have mainly been conducted in Western populations, and comprehensive data from Asia are limited. To address this gap, we analyzed 242 MB cases collected from 39 institutions through the Japan Pediatric Molecular Neuro-Oncology Group, performing centralized molecular classification using NanoString-based gene expression profiling, DNA methylation arrays,...