Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants.

The protein tyrosine phosphatase SHP2, encoded by , is an important regulator of Ras/MAPK signaling that acts downstream of receptor tyrosine kinases and other transmembrane receptors. Germline mutations cause developmental disorders such as Noonan Syndrome, whereas somatic mutations drive various cancers. While many pathogenic mutations enhance SHP2 catalytic activity, others are inactivating or affect protein interactions, confounding our understanding of SHP2-driven disease.

Spatiotemporal Single-Cell Analysis Reveals T Cell Clonal Dynamics and Phenotypic Plasticity in Human Graft-versus-Host Disease.

Allogeneic hematopoietic cell transplantation (alloHCT) is curative for various hematologic diseases but often leads to acute graft-versus-host disease (GVHD), a potentially life-threatening complication. We leverage GVHD as a uniquely tractable disease model to dissect complex T-cell-mediated pathology in 27 alloHCT recipients. We integrate pre-transplant identification of alloreactive T-cells with longitudinal tracking across blood and gut, using mixed lymphocyte reaction-based clonal "fingerprinting", TCR clonotyping, single-cell RNA/TCR sequencing, and spatial transcriptomics.

Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4.

Background: Astrocytoma, isocitrate dehydrogenase-mutant, WHO grade 4 (Astro4), is a new tumor type in the 2021 WHO classification of central nervous system tumors that has been poorly characterized in the literature. This study evaluates predictors of prognosis in a large cohort of newly diagnosed Astro4.

Methods: We retrospectively identified 128 consecutive adult patients who presented with an initial diagnosis of Astro4 at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2010 and 2021.

Advancing β-adrenoreceptor agonism for recovery after volumetric muscle loss through regenerative rehabilitation and biomaterial delivery approaches.

Volumetric muscle loss (VML) injury results in the unrecoverable loss of muscle mass and contractility. Oral delivery of formoterol, a β-adrenergic receptor agonist, produces a modest recovery of muscle mass and contractility in VML-injured mice. The objective of this study was to determine if a regenerative rehabilitation paradigm or a regenerative medicine paradigm could enhance the recovery of VML-injured muscle.

lioma esource utreach ith upport: A program to identify and initiate supportive care interventions for unmet needs among adult lower-grade glioma patients.

Background: Lower-grade (WHO grades 2-3) gliomas typically affect young and middle-aged adults and exhibit () mutations. For such patients, symptoms related to the tumor and associated treatment contribute to morbidity and erode quality of life. With improved treatment, a better understanding of these effects over time is critically needed.