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Experiencing a mental health crisis has a detrimental impact on a patient’s life. A machine learning algorithm trained retrospectively with electronic health records can predict almost 60% of mental health crises 4 weeks in advance. Prospective evaluation of the algorithm in clinical practice reveals its potential to enable preemptive interventions.
Phenotypic heterogeneity in type 2 diabetes (T2D) was visualized by non-linear dimensionality reduction in a cohort of over 23,000 people. Variation in the T2D phenotype mapped to variation in drug response, risk of disease complications and underlying genetic architecture.
PIK3CA gain-of-function mutations are among the most common alterations in human solid cancers. Through the use of stimulation-induced functional T cell receptor (TCR) sequencing (SIFT-seq), a panel of TCRs that bind a mutant PI3Kα shared neoantigen was identified, including a potential clinical candidate that engages cancer cells via a distinctive CDR3β loop.
Clinical trial results show that psilocybin, a potent psychedelic, has antidepressant effects in patients with depression and is more effective than escitalopram. Functional MRI experiments revealed a decrease in brain modularity after psilocybin therapy, indicative of an increase in the global integration of the brain’s functional networks.
Secretion of S100A9 by brain metastatic cells activates radioresistance. Blood S100A9 could be used as a biomarker to predict responses to irradiation and to guide a combination therapy with a radiosensitizer.
The largest metabolomic study of asthma thus far, comprising >14,000 people from four independent cohorts, has found that inhaled corticosteroid (ICS) treatment is associated with adrenal suppression, even at low doses. Thus, ICS dosage should be optimized to minimize adrenal suppression while maintaining its established benefits in asthma management.
The developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia (B-ALL) was identified by comparison of bulk and single-cell leukemia transcriptomes with those of a human fetal bone marrow reference. Unlike standard-risk childhood B-ALL, this aggressive leukemia was characterized by early lymphocyte precursor (ELP) differentiation. Moreover, in contrast to healthy ELPs, KMT2A-rearranged infant B-ALL cells had both myeloid and lymphoid features and expressed potentially targetable novel combinations of antigens.
Analyses of primary myelodysplastic syndrome (MDS) samples from the largest cohort ever evaluated demonstrate that the hematopoietic stem cell populations that originate MDS have distinct differentiation phenotypes and associated signaling pathways. These differences can be targeted with selective therapies that could benefit patients with progressed disease.
Bone marrow transplantation causes peripheral cells to engraft the brain by an unclear mechanism. Microglia, the brain’s immune cells, lose their regenerative capacity when the bone marrow transplantation chemotherapy agent busulfan arrests their cell cycle. This causes a gradual decrease in microglial density, creating a niche for peripheral donor cells to engraft the brain and become resident macrophages.
