Matrix metalloproteinase 9: An emerging biomarker for classification of adherent vestibular schwannoma.

Background: The progression of vestibular schwannoma (VS) is intricately linked with interactions between schwannoma cells and the extracellular matrix. Surgical resection of VS is associated with substantial risks as tumors are adherent to the brainstem and cranial nerves. We evaluate the role of matrix metalloproteinase 9 (MMP9) in VS and explore its potential as a biomarker to classify adherent VS.

Exploring a distinct FGFR2::DLG5 rearrangement in a low-grade neuroepithelial tumor: A case report and mini-review of protein fusions in brain tumors.

We report the novel clinical presentation of a primary brain neoplasm in a 30-year-old man with a mass-like area in the anteromedial temporal lobe. Histopathological analysis revealed a low-grade neuroepithelial tumor with cytologically abnormal neurons and atypical glial cells within the cerebral cortex. Molecular analysis showed a previously undescribed FGFR2::DLG5 rearrangement.

Proteomic Analysis of Spatial Heterogeneity Identifies HMGB2 as Putative Biomarker of Tumor Progression in Adult-Type Diffuse Astrocytomas.

Although grading is defined by the highest histological grade observed in a glioma, most high-grade gliomas retain areas with histology reminiscent of their low-grade counterparts. We sought to achieve the following: (i) identify proteins and molecular pathways involved in glioma evolution; and (ii) validate the high mobility group protein B2 (HMGB2) as a key player in tumor progression and as a prognostic/predictive biomarker for diffuse astrocytomas. We performed liquid chromatography tandem mass spectrometry (LC-MS/MS) in multiple areas of adult-type astrocytomas and validated our finding in multiplatform-omics studies and high-throughput IHC analysis.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care.

Identifying Tumor Microenvironment Biomarkers in Adherent and Cystic Vestibular Schwannomas.

Objective: A subset of vestibular schwannomas (VSs), including cystic tumors, have higher postoperative morbidity because of the presence of adhesions between the tumor, facial nerve (FN), and brainstem. We identify tumor microenvironment (TME) biomarkers to better classify these tumors and predict the degree of tumor adherence.

Study Design: Retrospective case series.

Glioblastoma pseudoprogression and true progression reveal spatially variable transcriptional differences.

Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma follow-up. However, treatment-related pseudoprogression presents with similar imaging features but requires different clinical management. While pathologic diagnosis is the gold standard to differentiate true progression and pseudoprogression, the lack of objective clinical standards and admixed histologic presentation creates the needs to (1) validate the accuracy of current approaches and (2) characterize differences between these entities to objectively differentiate true disease.

The Cognitive Framework Behind Modern Neuropathology.

Context: In 2021 the World Health Organization distributed a new classification of central nervous system tumors that incorporated modern testing modalities in the diagnosis. Although universally accepted as a scientifically superior system, this schema has created controversy because its deployment globally is challenging in the best of circumstances and impossible in resource-poor health care ecosystems. Compounding this problem is the significant challenge that neuropathologists with expertise in central nervous system tumors are rare.

DNA-caged nanoparticles electrostatic self-assembly.

DNA-modified nanoparticles enable DNA sensing and therapeutics in nanomedicine and are also crucial for nanoparticle self-assembly with DNA-based materials. However, methods to conjugate DNA to nanoparticle surfaces are limited, inefficient, and lack control. Inspired by DNA tile nanotechnology, we demonstrate a new approach to nanoparticle modification based on electrostatic attraction between negatively charged DNA tiles and positively charged nanoparticles.

Evaluating glioblastoma tumour sphere growth and migration in interaction with astrocytes using 3D collagen-hyaluronic acid hydrogels.

Glioblastoma (GB) is an astrocytic brain tumour with a low survival rate, partly because of its highly invasive nature. The GB tumour microenvironment (TME) includes its extracellular matrix (ECM), a variety of brain cell types, unique anatomical structures, and local mechanical cues. As such, researchers have attempted to create biomaterials and culture models that mimic features of TME complexity.

Unsupervised machine learning models reveal predictive markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Purpose: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care.

Microglia are implicated in the development of paclitaxel chemotherapy-associated cognitive impairment in female mice.

Chemotherapy remains a mainstay in the treatment of many types of cancer even though it is associated with debilitating behavioral side effects referred to as "chemobrain," including difficulty concentrating and memory impairment. The predominant hypothesis in the field is that systemic inflammation drives these cognitive impairments, although the brain mechanisms by which this occurs remain poorly understood. Here, we hypothesized that microglia are activated by chemotherapy and drive chemotherapy-associated cognitive impairments.

mutation mediated by expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia.

Mutations in the transcription factor cause congenital central hypoventilation syndrome (CCHS). The syndrome is characterized by hypoventilation and inability to regulate breathing to maintain adequate O and CO levels. The mechanism by which CCHS impact respiratory control is incompletely understood, and even less is known about the impact of the non-polyalanine repeat expansion mutations (NPARM) form.

Regulation of blood vessels by ATP in the ventral medullary surface in a rat model of Parkinson's disease.

Parkinson's disease (PD) patients often experience impairment of autonomic and respiratory functions. These include conditions such as orthostatic hypotension and sleep apnea, which are highly correlated with dysfunctional central chemoreception. Blood flow is a fundamental determinant of tissue CO/H, yet the extent to which blood flow regulation within chemoreceptor regions contributes to respiratory behavior during neurological disease remains unknown.

Information theory approaches to improve glioma diagnostic workflows in surgical neuropathology.

Aims: Resource-strained healthcare ecosystems often struggle with the adoption of the World Health Organization (WHO) recommendations for the classification of central nervous system (CNS) tumors. The generation of robust clinical diagnostic aids and the advancement of simple solutions to inform investment strategies in surgical neuropathology would improve patient care in these settings.

Methods: We used simple information theory calculations on a brain cancer simulation model and real-world data sets to compare contributions of clinical, histologic, immunohistochemical, and molecular information.

Astrocyte regional heterogeneity revealed through machine learning-based glial neuroanatomical assays.

Evaluation of reactive astrogliosis by neuroanatomical assays represents a common experimental outcome for neuroanatomists. The literature demonstrates several conflicting results as to the accuracy of such measures. We posited that the diverging results within the neuroanatomy literature were due to suboptimal analytical workflows in addition to astrocyte regional heterogeneity.

Revisiting the Neuropathology of Sudden Infant Death Syndrome (SIDS).

Sudden infant death syndrome (SIDS) is one of the leading causes of infant mortality in the United States (US). The extent to which SIDS manifests with an underlying neuropathological mechanism is highly controversial. SIDS correlates with markers of poor prenatal and postnatal care, generally rooted in the lack of access and quality of healthcare endemic to select racial and ethnic groups, and thus can be viewed in the context of health disparities.

Machine learning-based data analytic approaches for evaluating post-natal mouse respiratory physiological evolution.

Respiratory parameters change during post-natal development, but the nature of their changes have not been well-described. The advent of commercially available plethysmographic instruments provided improved repeatability of measurements and standardization of measured breathing in mice across laboratories. These technologies thus allowed for exploration of more precise respiratory pattern changes during the post-natal developmental epoch.

Hyaluronic acid induces ROCK-dependent amoeboid migration in glioblastoma cells.

Glioblastoma (GBM) is the most aggressive and deadly adult brain tumor, primarily because of its high infiltrative capacity and development of resistance to therapy. Although GBM cells are typically believed to migrate via mesenchymal (e.g.

Neonatal apneic phenotype in a murine congenital central hypoventilation syndrome model is induced through non-cell autonomous developmental mechanisms.

Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO and/or O respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS.

Stimulation of retrotrapezoid nucleus Phox2b-expressing neurons rescues breathing dysfunction in an experimental Parkinson's disease rat model.

Emerging evidence from multiple studies indicates that Parkinson's disease (PD) patients suffer from a spectrum of autonomic and respiratory motor deficiencies in addition to the classical motor symptoms attributed to substantia nigra degeneration of dopaminergic neurons. Animal models of PD show a decrease in the resting respiratory rate as well as a decrease in the number of Phox2b-expressing retrotrapezoid nucleus (RTN) neurons. The aim of this study was to determine the extent to which substantia nigra pars compact (SNc) degeneration induced RTN biomolecular changes and to identify the extent to which RTN pharmacological or optogenetic stimulations rescue respiratory function following PD-induction.

Neuropathologists play a key role in establishing the extent of COVID-19 in human patients.

SARS-CoV2 infection causes COVID-19, and represents the most emergent health care crisis of our generation. Ample evidence in the scientific literature suggests that SARS-CoV, MERS-CoV, and endemic human coronaviruses infect brain cells. We delineate a rationale for encouraging evaluation of the brain, and in particular the brainstem, in COVID-19 so that potential neuropathological mechanisms can be delineated.

Near field non-invasive electrophysiology of retrotrapezoid nucleus using amperometric cation sensor.

Central chemoreception is the process whereby the brainstem senses blood gas levels and adjusts homeostatic functions such as breathing and cardiovascular tone accordingly. Rodent evidence suggests that the retrotrapezoid nucleus (RTN) is a master regulator of central chemoreception, in particular, through direct sensation of acidosis induced by CO levels. The oscillatory dynamics caused by pH changes as sensed by the RTN surface and its relationship to the fluctuations in cation flux is not clearly understood due to the current limitations of electrophysiology tools and this article presents our investigations to address this need.

MicroRNA-mRNA Interactions at Low Levels of Compressive Solid Stress Implicate mir-548 in Increased Glioblastoma Cell Motility.

Glioblastoma (GBM) is an astrocytic brain tumor with median survival times of <15 months, primarily as a result of high infiltrative potential and development of resistance to therapy (i.e., surgical resection, chemoradiotherapy).