Citations

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

Objective We sought to characterize factors associated with postoperative complications in patients undergoing primary cleft lip repair (CLR). Design The National Surgical Quality Improvement Program-Pediatric database was queried to identify patients under 12 months old undergoing CLR using CPT codes. Multivariable analysis was conducted to characterize complications and associated comorbidities. Setting A multicenter sample. Patients/Participants A total of 11 957 cases (81.9% unilateral CLR and 18.1% bilateral CLR) were identified. Interventions None. Main Outcomes/Measures The postoperative outcomes of significance were surgical site infection (SSI), wound dehiscence, and unplanned reintubation within 30 days of CLR. Results The cohort had a mean age of 4.7 ± 2.0 months and a median American Society of Anesthesiologists classification of 2. SSIs occurred in 0.6% of cases and were independently associated with bilateral cleft anatomy (OR 2.16, P = .003) and longer anesthesia time (OR per minute: 1.004, P = .009). Wound dehiscence occurred in 0.4% of patients and was independently associated with bilateral cleft anatomy (OR 4.03, P < .001) but was associated with shorter anesthesia duration (OR per minute: 0.991, P < .001). Unplanned reintubation occurred in 0.2% of cases, with these patients having significantly higher rates of multiple comorbidities. Conclusion Wound dehiscence, SSI, and unplanned reintubation were rare complications following CLR. Patients with a bilateral cleft lip had increased odds of both SSI and wound dehiscence.

A growing number of data-driven clinical decision support (CDS) tools are incorporated into tele-critical care, but the clinician perceptions of their utility are largely unknown. The objective of this web-based survey study was to understand the perceived utility of data-driven CDS in tele-critical care. The survey had 158 respondents (1.1% response rate), with 51.3% stating they currently use a data-driven CDS tool. Of those who responded about the impact of data-driven CDS, most (62.0%) reported a meaningful impact on workup, evidence-based care, or patient outcomes. Survey participants found CDS most useful if they or their colleagues had positive experiences with it, especially if it was responsible for improved patient outcomes. Thus, data-driven CDS is perceived useful for tele-critical care services.

Abstract In Alzheimer’s disease (AD), tau pathology arises in entorhinal cortex layer II (ECII) and advances through defined hippocampal circuits to CA1 and connected neocortical regions, yet the determinants of this hierarchical spread remain unclear. We previously established a circuit-defined propagation model by expressing Cre-inducible human P301L 2N4R tau selectively in Wolframin-1 (Wfs1) + ECII neurons using AAV-FLEX-Tau P301L in Wfs1-Cre mice. Here, to test how amyloid-β (Aβ) and human tau background shape propagation, we generated human MAPT knock-in Wfs1 mice and APP NL-G-F / MAPT double knock-in Wfs1 mice (T-Wfs1 and AT-Wfs1) and induced ECII-restricted Tau P301L expression. Three months after injection, phosphorylated or misfolded tau-positive neurons were enriched in proximal CA1 in Wfs1 and T-Wfs1 mice, resembling primary age-related tauopathy, whereas AT-Wfs1 mice showed preferential accumulation near the CA1/subiculum (Sub) boundary, consistent with an AD-like pattern. In T-Wfs1 and AT-Wfs1 mice, tau spread extended through Sub to neocortical regions, and phosphorylated tau accumulated predominantly in excitatory rather than inhibitory neurons. Electrophysiological analyses revealed increased spontaneous neuronal firing and impaired GABAergic transmission in the CA1/Sub boundary and neocortical areas in T-Wfs1 and AT-Wfs1 mice, indicative of impaired GABAergic input and enhanced neuronal excitability in these regions. Together, these data indicate that human MAPT and Aβ pathology shift the circuit topography of tau propagation and are associated with early network dysfunction, supporting a synergistic interaction that promotes AD-like spread and synaptic imbalance.