Publications

CONCLUSION: These data provide in vivo evidence that anti-TNF, but not anti-IL-12/23, therapy impairs the quantity and quality of antigen-specific GC outputs in humans.

Monkeypox virus (MPXV) is emerging as a major concern in the field of infectious diseases. Current treatments are limited, highlighting the need for new therapeutic options. The use of computational methods, such as molecular docking and molecular dynamic (MD) simulations, is a valuable approach in identifying potential compounds that can target specific proteins of the virus, like the DNA polymerase and profilin-like protein profilin-like protein A42R (A42R) in this case, with the aim of...

Growth-limiting droughts (GLD) impair tissue expansion and delay developmental transitions but are often not considered as stressors, as many physiological traits are only slightly altered relative to well-watered counterparts. Concurrently, cell size, biochemical makeup, and transcriptome profiles vary along the leaf blade in accordance with the partitioning of distinct functions to spatially defined regions of the leaf. This suggests that because different parts of the leaf have underlying...

CONCLUSIONS: Altogether, these findings suggest that monoallelic loss of function variants in DENND2B cause a novel autosomal dominant neurodevelopmental disorder with variable vulnerability for psychosis and/or catatonia.

BACKGROUND: There is considerable variability in how older adults with cancer tolerate and recover from surgery and systemic treatments. A greater understanding of individual trajectories is crucial in guiding personalized treatment decisions. Frailty may explain these inter-individual differences. Despite emerging evidence on the association between perioperative frailty assessment and outcomes after noncardiac surgery, there is limited data in gynecologic oncology. A perioperative...

The treatment of neurovascular disease in children continues to push clinical and innovative boundaries, carrying with them uniquely high stakes. Hemorrhage from, or occlusion of, a major cerebral blood vessel may result in devastating neurological injury or death. In children and young people, the stakes around a decision to offer or withhold treatment are even greater. The implications of long-term neurodisability in a young child who may live for many decades with the aftermath of brain...

Through international gene-matching efforts, we identified 10 individuals with ultrarare heterozygous variants, including 5 de novo variants, in BMAL1, a core component of the molecular clock. Instead of an isolated circadian phenotype seen with disease-causing variants in other molecular clock genes, all individuals carrying BMAL1 variants surprisingly share a clinical syndrome manifest as developmental delay and autism spectrum disorder, with variably penetrant sleep disturbances, seizures,...

Congenital heart disease (CHD) is the most common type of birth defects in humans. Genetic factors have been identified as an important contributor to the etiology of CHD. However, the underlying genetic causes in most individuals remain unclear. Here, 101 individuals with CHD and their unaffected parents were included in this study. Chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic tool was applied for all affected individuals, followed by trio-based whole exome...

RNA-binding proteins (RBPs) are key regulators of gene expression; however, their RNA-binding specificities, that is, motifs, have not been comprehensively determined. Here we introduce Eukaryotic Protein-RNA Interactions (EuPRI), a freely available resource of RNA motifs for 34,746 RBPs from 690 eukaryotes. EuPRI includes in vitro binding data for 504 RBPs, including newly collected RNAcompete data for 174 RBPs, along with thousands of predicted motifs. We predict these motifs with an...

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and...

INTRODUCTION: Neuroinflammation, a key player in Alzheimer's disease (AD) pathogenesis, may be differentially involved in young-onset (YOAD) compared to late-onset (LOAD) AD.

The Fifth International Symposium on Fungal Stress (ISFUS) brought together in Brazil many of the leaders in the field of fungal stress responses, from fourteen countries, for four days of outstanding science ranging from basic research to studies with agricultural, medical, industrial, and environmental significance. In addition to the excellent oral and poster presentations, the Symposium organisers ensured that all participants had ample opportunity to engage, socialise, and network to...

Facial expressions are fundamental to social communication, with emotional face processing developing throughout childhood. However, the neural mechanisms underlying this process in young children remain underexplored due to challenges in neuroimaging this population. Optically pumped magnetometers (OPMs), a wearable magnetoencephalography (MEG) technology, offer potential advantages for studying these responses early in life. This study investigated evoked responses and functional connectivity...

CONCLUSIONS: Achieving standardization of EEG procedures in multi-site studies is essential for the successful implementation of biomarker-informed clinical trials.

CONCLUSIONS: This study identifies conserved cell cycle regulators underlying efficient liver regeneration and provides a predictive framework for evaluating regenerative capacity. The integration of deep learning and multi-omics profiling provides a promising approach to better understand liver regeneration and may help guide therapeutic strategies, especially in complex clinical settings.

Passive and task-based MEG responses have been extensively studied in clinical populations to identify signatures that could serve as markers for clinical diagnosis or to monitor progression of treatment. Establishing the reliability of these responses across repeat testing as a benchmark is therefore essential. Emerging MEG technology using optically pumped magnetometers (OPMs) promises a new era for MEG, enhancing both research capabilities and clinical applications. However, the test-retest...

Target 2035 is a global initiative that aims to develop a potent and selective pharmacological modulator, such as a chemical probe, for every human protein by 2035. Here, we describe the Target 2035 roadmap to develop computational methods to improve small-molecule hit discovery, which is a key bottleneck in the discovery of chemical probes. Large, publicly available datasets of high-quality protein-small-molecule binding data will be created using affinity-selection mass spectrometry and...

This paper reports the findings of an international survey of health data ecosystems (HDEs) in 12 countries plus the H3 Africa project using live, structured interviews with senior project team members under the auspices of Canada's All for One Precision Health Initiative. We note the high level of interest in HDEs around the world, as well as in Canada, despite the financial, jurisdictional, and other barriers that continue to hold back widespread data sharing. We present results detailing...

Adoptive T cell therapies have therapeutic potential for treating solid tumors, but long-term efficacy is limited by reduced functional fitness and poor persistence within the tumor microenvironment. Here we show that intratumoral T cells undergo translatome remodeling, transitioning into a hypertranslational state as they acquire dysfunctional traits. The RNA-binding protein LARP4 is a translation regulator that drives hypertranslation and dysfunction by selectively enhancing the translation of...

CONCLUSIONS: These data support providers in counselling families regarding the importance of annual COVID-19 booster vaccines in children with IMID.