Single-Cell Heterogeneity of EGFR Pathway Is Linked to Unique Signatures of Drug Response and Malignancy in Patient Derived Glioblastoma Stem Cells.

Purpose: In glioblastoma, the therapeutically intractable and resistant phenotypes can be derived from glioma stem cells, which often have different underlying mechanisms from non-stem glioma cells. Aberrant signaling across the EGFR-PTEN-AKT-mTOR pathways have been shown as common drivers of glioblastoma. Revealing the inter and intra-cellular heterogeneity within glioma stem cell populations in relations to signaling patterns through these pathways may be key to precision diagnostic and therapeutic targeting of these cells.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

The Neurologist's Role in Promoting Brain Health: Emerging Issues in Neurology.

Neurologic conditions are a leading cause of morbidity and mortality within the United States and worldwide. Brain health is a global concern, and the American Academy of Neurology's Brain Health Initiative promises to drive progress in this field over the next decades. Neurologists with detailed training and insight into brain function are uniquely positioned to apply emerging preventive health data to promote healthy brain development and maintain optimal brain function throughout the lifespan.

Financial strain measures and associations with adult health: A systematic literature review.

Despite growing attention to other social needs like food and housing insecurity, financial strain, defined as having difficulty making ends meet or lacking money for basic needs, is under-recognized. Inconsistent labels and measures have made the literature difficult to unify. We used many synonyms for financial strain to systematically identify 199 U.

Results From a Randomized Trial of Intensive Glucose Management Using CGM Versus Usual Care in Hospitalized Adults With Type 2 Diabetes: The TIGHT Study.

Objective: To evaluate whether continuous glucose monitoring (CGM) could assist providers in intensifying glycemic management in hospitalized patients with type 2 diabetes.

Research Design And Methods: At six academic hospitals, adults with type 2 diabetes hospitalized in a non-intensive care setting were randomly assigned to either standard therapy with glucose target 140-180 mg/dL (standard group) or intensive therapy with glucose target 90-130 mg/dL guided by CGM (intensive group). The primary outcome was mean glucose measured with CGM (blinded in standard group), and the key secondary outcome was CGM glucose <54 mg/dL.

Elucidation of the Transformation of Coordination Polymer Intermediates into 2D Metal-Organic Framework Films during Chemical Vapor Deposition.

Chemical vapor deposition (CVD) is a rising tool to synthesize metal-organic framework (MOF) films. Despite growing interest and usage, its mechanism is less known. Especially, the identification of intermediates is crucial for understanding the growth mechanism and further controlling their structures.

The neurocognitive correlates of DTI indicators of white matter disorganization in pediatric moderate-to-severe traumatic brain injury.

Introduction: Neuroimaging has expanded our understanding of pediatric brain disorders in which white matter organization and connectivity are crucial to functioning. Paralleling the known pathobiology of many neurodevelopmental disorders, traumatic brain injury (TBI) in childhood can alter trajectories of brain development. Specifically, diffusion tensor imaging (DTI) studies in TBI have demonstrated white matter (WM) abnormalities that suggest microstructural disruptions that may underlie atypical neurodevelopment.

Pressure enabled organic reactions via confinement between layers of 2D materials.

Confinement of reactants within nanoscale spaces of low-dimensional materials has been shown to provide reorientation of strained reactants or stabilization of unstable reactants for synthesis of molecules and tuning of chemical reactivity. While few studies have reported chemistry within zero-dimensional pores and one-dimensional nanotubes, organic reactions in confined spaces between two-dimensional materials have yet to be explored. Here, we demonstrate that reactants confined between atomically thin sheets of graphene or hexagonal boron nitride experience pressures as high as 7 gigapascal, which allows the propagation of solvent-free organic reactions that ordinarily do not occur under standard conditions.

FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase 1 Mutation.

On December 1, 2022, the FDA approved the new molecular entity olutasidenib (Rezlidhia, Rigel Pharmaceuticals), a small-molecule inhibitor of isocitrate dehydrogenase 1, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase 1 mutation as detected by an FDA-approved test. The efficacy of olutasidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion of transfusion dependence to transfusion independence in Study 2102-HEM-101. In the pivotal trial, 147 adult patients treated with 150 mg twice daily of olutasidenib were evaluable for efficacy.

Implementation and validation of face de-identification (de-facing) in ADNI4.

Introduction: Recent technological advances have increased the risk that de-identified brain images could be re-identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de-identified brain imaging, who quickly acted to protect participants' privacy.

Methods: An independent expert committee evaluated 11 face-deidentification ("de-facing") methods and selected four for formal testing.

A multispecific antibody against SARS-CoV-2 prevents immune escape in vitro and confers prophylactic protection in vivo.

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies.

The Road More or Less Traveled- Examining the Role of Consolidative Allogeneic Hematopoietic Stem Cell Transplantation After Chimeric Antigen Receptor T Cell Therapy in B-cell ALL.

Treatment with CD19-targeted chimeric antigen receptor T cell therapy (CD19-CART) has improved salvage rates in children and adults with relapsed and/or refractory B-cell acute lymphoblastic leukemia (ALL). However, not all patients treated with CD19-CAR T cells achieve long-term remission. The role of allogeneic hematopoietic stem cell transplantation as consolidative therapy remains undefined.

SARS-CoV-2 ferritin nanoparticle vaccines produce hyperimmune equine sera with broad sarbecovirus activity.

The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4.

Histopathological correlations of CT-based radiomics imaging biomarkers in native kidney biopsy.

Background: Kidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade.

Antibody sequence determinants of viral antigen specificity.

Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, antigen-specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence.

CAR T cell therapy for pediatric central nervous system tumors: a review of the literature and current North American trials.

Central nervous system (CNS) tumors are the leading cause of cancer-related death in children. Typical therapy for CNS tumors in children involves a combination of surgery, radiation, and chemotherapy. While upfront therapy is effective for many high-grade tumors, therapy at the time of relapse remains limited.

Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

Background: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors.

Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report.

Rationale: Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma.

Development of a diamagnetic loop in KAIMIR.

We developed a diamagnetic loop for the estimation of plasma stored energy in the KAIST Magnetic Mirror magnetic mirror device [Oh et al., J. Plasma Phys.

Photocatalytic Conversion of CO to Formate/CO by an (η--Cymene)Ru(II) Half-Metallocene Catalyst: Influence of Additives and TiO Immobilization on the Catalytic Mechanism and Product Selectivity.

The catalytic efficacy of the monobipyridyl (η--Cymene)Ru(II) half-metallocene, [(-Cym)Ru(bpy)Cl] was evaluated in both mixed homogeneous (dye + catalyst) and heterogeneous hybrid systems (dye/TiO/Catalyst) for photochemical CO reduction. A series of homogeneous photolysis experiments revealed that the (-Cym)Ru(II) catalyst engages in two competitive routes for CO reduction (CO to formate conversion via Ru-hydride vs CO to CO conversion through a Ru-COOH intermediate). The conversion activity and product selectivity were notably impacted by the p value and the concentration of the proton source added.

Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.

Background: Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening.

Growth of diamond in liquid metal at 1 atm pressure.

Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. ). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon.