Single-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution.

The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.

Highly multiplexed imaging reveals prognostic immune and stromal spatial biomarkers in breast cancer.

Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.

In situ detection of individual classical MHC-I gene products in cancer.

Tumor-specific HLA class I expression is required for cytotoxic T-cell elimination of cancer cells expressing tumor-associated or neo-antigens. Cancers downregulate antigen presentation to avoid adaptive immunity. The highly polymorphic nature of the genes encoding these proteins, coupled with quaternary-structure changes after formalin fixation, complicate detection by immunohistochemistry.

Moving Beyond Teaching Skill Curriculum: Development of a Distinction in Medical Education Track.

Background: Most postgraduate medical education tracks are faculty-led and emphasise teaching skills. A peer-to-peer medical education track focused on curriculum development and scholarship is notably underrepresented in the literature, especially within graduate medical education. To address these gaps, a 2-year Distinction in Medical Education (DIME) track was developed.

Cerebral cavernous malformation with associated Streptococcus pyogenes abscess in a child: a case report and literature review.

Cerebral cavernous malformations (CCMs) are angiographically occult vascular lesions that present with a variety of neurological symptoms, including seizures, features of raised intracranial pressure and focal neurological deficits. In extremely rare circumstances, CCMs have presented with concomitant brain abscess formation. To date, five cases have previously been reported, the majority of which have affected patients aged 16 years or older.