Gliomagenesis mimics an injury response orchestrated by neural crest-like cells.

Glioblastoma is an incurable brain malignancy. By the time of clinical diagnosis, these tumours exhibit a degree of genetic and cellular heterogeneity that provides few clues to the mechanisms that initiate and drive gliomagenesis. Here, to explore the early steps in gliomagenesis, we utilized conditional gene deletion and lineage tracing in tumour mouse models, coupled with serial magnetic resonance imaging, to initiate and then closely track tumour formation.

Spatial Transcriptomics Reveals the Temporal Architecture of the Seminiferous Epithelial Cycle and Precise Sertoli-Germ Synchronization.

Spermatogenesis is characterized by the seminiferous epithelial cycle, a periodic pattern of germ cell differentiation with a wave-like progression along the length of seminiferous tubules. While key signaling and metabolic components of the cycle are known, the transcriptional changes across the cycle and the correlations between germ cell and somatic lineages remain undefined. Here, we use spatial transcriptomics via RNA SeqFISH+ to profile 2,638 genes in 216,090 cells in mouse testis and identify a periodic transcriptional pattern across tubules that precisely recapitulates the seminiferous epithelial cycle, enabling us to map cells to specific timepoints along the developmental cycle.

Haemophilus influenzae Type b Vaccine Immunogenicity in American Indian/Alaska Native Infants.

Objectives: American Indian and Alaska Native (AI/AN) infants historically experienced a disproportionate burden of invasive Haemophilus influenzae type b (Hib) disease, especially early in life. PedvaxHIB vaccine is preferentially recommended for AI/AN infants because it elicits protective antibody levels postdose 1. Vaxelis, a hexavalent vaccine that contains the same Hib conjugate as PedvaxHIB but at lower concentration, is recommended for US children, but postdose 1 Hib immunogenicity data are needed to inform whether a preferential recommendation should be made for AI/AN infants.

Mechanisms that clear mutations drive field cancerization in mammary tissue.

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1;Trp53 cells, and find that both follow a similar pattern of loss and spread within ducts.

Dynamic regulation of tissue fluidity controls skin repair during wound healing.

During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging.

Lemierre's syndrome presenting with arterial and Central nervous system involvement.

A 17-year-old male presented with acute onset right-sided facial swelling, trismus, pharyngitis, and sepsis. An initial CT abdomen and pelvis revealed multifocal bilateral nodular cavitary lung lesions. CT soft tissue neck with contrast demonstrated a parapharyngeal abscess and thrombophlebitis of the right internal jugular vein.

Factors Associated With Hepatitis A Seropositivity at 23 Years After Childhood Vaccination.

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years.

Atypical low-frequency cortical encoding of speech identifies children with developmental dyslexia.

Slow cortical oscillations play a crucial role in processing the speech amplitude envelope, which is perceived atypically by children with developmental dyslexia. Here we use electroencephalography (EEG) recorded during natural speech listening to identify neural processing patterns involving slow oscillations that may characterize children with dyslexia. In a story listening paradigm, we find that atypical power dynamics and phase-amplitude coupling between delta and theta oscillations characterize dyslexic versus other child control groups (typically-developing controls, other language disorder controls).

Red2Flpe-SCON: a versatile, multicolor strategy for generating mosaic conditional knockout mice.

Image-based lineage tracing enables tissue turnover kinetics and lineage potentials of different adult cell populations to be investigated. Previously, we reported a genetic mouse model system, Red2Onco, which ectopically expressed mutated oncogenes together with red fluorescent proteins (RFP). This system enabled the expansion kinetics and neighboring effects of oncogenic clones to be dissected.

Adult Human, but Not Rodent, Spermatogonial Stem Cells Retain States with a Foetal-like Signature.

Spermatogenesis involves a complex process of cellular differentiation maintained by spermatogonial stem cells (SSCs). Being critical to male reproduction, it is generally assumed that spermatogenesis starts and ends in equivalent transcriptional states in related species. Based on single-cell gene expression profiling, it has been proposed that undifferentiated human spermatogonia can be subclassified into four heterogenous subtypes, termed states 0, 0A, 0B, and 1.

International circumpolar surveillance: update on the interlaboratory quality control program for , 2009 to 2020.

Unlabelled: The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba.

serotype 3 population structure in the era of conjugate vaccines, 2001-2018.

Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.

Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence.

Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist for decades, providing antigen-specific long-term protection. We developed a mathematical framework to explore the dynamics of plasma cell removal and its regulation by survival factors. Analyses of antibody persistence following hepatitis A and B and HPV vaccination revealed specific patterns of longevity and heterogeneity within and between responses, implying that this process is fine-tuned near a critical "flat" state between two dynamic regimes.

Disentangling trust of patients with rare cancer in their healthcare professionals and the healthcare system: a qualitative interview study.

Purpose: Patients with a rare cancer face challenges, e.g., delayed diagnosis, that may affect trust in the healthcare system and the healthcare professionals (HCPs) involved.

Understanding the cell fate and behavior of progenitors at the origin of the mouse cardiac mitral valve.

Congenital heart malformations include mitral valve defects, which remain largely unexplained. During embryogenesis, a restricted population of endocardial cells within the atrioventricular canal undergoes an endothelial-to-mesenchymal transition to give rise to mitral valvular cells. However, the identity and fate decisions of these progenitors as well as the behavior and distribution of their derivatives in valve leaflets remain unknown.

Beyond Average: α-Particle Distribution and Dose Heterogeneity in Bone Metastatic Prostate Cancer.

α-particle emitters are emerging as a potent modality for disseminated cancer therapy because of their high linear energy transfer and localized absorbed dose profile. Despite great interest and pharmaceutical development, there is scant information on the distribution of these agents at the scale of the α-particle pathlength. We sought to determine the distribution of clinically approved [Ra]RaCl in bone metastatic castration-resistant prostate cancer at this resolution, for the first time to our knowledge, to inform activity distribution and dose at the near-cell scale.

Rate and durability of the clearance of HBsAg in Alaska Native persons with long-term HBV infection: 1982-2019.

Background And Aims: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population.

Approach And Results: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019.

Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal.

The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized.

Wound-healing plasticity enables clonal expansion of founder progenitor cells in colitis.

Chronic colonic injury and inflammation pose high risks for field cancerization, wherein injury-associated mutations promote stem cell fitness and gradual clonal expansion. However, the long-term stability of some colitis-associated mutational fields could suggest alternate origins. Here, studies of acute murine colitis reveal a punctuated mechanism of massive, neutral clonal expansion during normal wound healing.

Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms.

Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes.

Cancers make their own luck: theories of cancer origins.

Cancer has been a leading cause of death for decades. This dismal statistic has increased efforts to prevent the disease or to detect it early, when treatment is less invasive, relatively inexpensive and more likely to cure. But precisely how tissues are transformed continues to provoke controversy and debate, hindering cancer prevention and early intervention strategies.

Spatial analysis of nanoparticle distribution in human breast xenografts reveals nanoparticles targeted to cancer cells localized with tumor-associated stromal cells.

The biological influence of physicochemical parameters of "targeted" nanoparticles on their delivery to cancer tumors remains poorly understood. A comparative analysis of nanoparticle distributions in tumors following systemic delivery across several models can provide valuable insights. Bionized nanoferrite nanoparticles (iron oxide core coated with starch), either conjugated with a targeted anti-HER2 antibody (BH), or unconjugated (BP), were intravenously injected into athymic nude or NOD-scid gamma (NSG) female mice bearing one of five human breast cancer tumor xenografts growing in a mammary fat pad.