Targeting tGLI1, a novel mediator of tumor therapeutic resistance, using Ketoconazole sensitizes glioblastoma to CDK4/6 therapy and chemoradiation.

Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with no effective treatments. While cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) show clinical promise in some cancers, they have not significantly improved survival in GBM patients. This lack of response is attributed to the treatment-resistant glioma stem cell (GSC) population.

A window-of-opportunity trial reveals mechanisms of response and resistance to navtemadlin in patients with recurrent glioblastoma.

Inhibitors of murine double minute homolog 2 (MDM2) represent a promising therapeutic approach for the treatment of wild-type glioblastomas (GBMs), reactivating p53 signaling to induce cancer cell death. We conducted a surgical window-of-opportunity trial (NCT03107780) of the MDM2 inhibitor navtemadlin (KRT-232) in 21 patients with wild-type recurrent GBM to determine achievable drug concentrations within tumor tissues and biological mechanisms of response and resistance. Participants received navtemadlin at 120 mg ( = 10) or 240 mg ( = 11) for 2 days before surgical resection and after surgery until progression or unacceptable toxicity.

Education Research: A Mixed-Methods Analysis of Journal Club Formats to Enhance Evidence-Based Practice Through Social Cognitive Learning Theory.

Background And Objectives: In an era of rapid advances in research, it is imperative for residents to develop the skills for evidence-based practice. Alternative journal club formats grounded in active learning strategies may be better suited to address this need, although evidence is lacking. A theoretical framework of social cognitive learning theory (SCLT) may provide insight into how journal clubs can be better designed to teach residents how to evaluate research.

Education Research: Use by Neurologists of Microteaching and Microassessment Programs for Teaching, Learning, and Patient Care Needs: A Qualitative Study.

Background And Objectives: Microlearning is the acquisition of knowledge or skills in small units, commonly delivered by digital technology. NeuroBytes (NB) and Question of the Day (QOD) are 2 microinstructional programs in neurology. NB programs are brief, video-based mini-courses on clinical topics (microteaching); QODs are daily multiple-choice questions (microassessment).

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Education Research: Introduction of a Standardized Communication Card to Facilitate Patient-as-Teacher Training for Medical Students in the Neurology Clerkship.

Background And Objectives: Enhanced communication has been recognized as an effective strategy to improve patient safety and care quality. While some communication skills can be taught in traditional didactic settings, learning from patient encounters is critical. Currently, patients are becoming increasingly involved as teachers for medical students within both the clinical and classroom setting.

Education Research: Competency-Based EEG Education: An Online Routine EEG Examination for Adult and Child Neurology Residents.

Background And Objectives: We recently published expert consensus-based curricular objectives for routine EEG (rEEG) interpretation for adult and child neurology residents. In this study, we used this curriculum framework to develop and validate an online, competency-based, formative and summative rEEG examination for neurology residents.

Methods: We developed an online rEEG examination consisting of a brief survey and 30 multiple-choice questions covering EEG learning objectives for neurology residents in 4 domains: normal, abnormal, normal variants, and artifacts.

Education Research: Evaluating Medical Student Learning Preference and Its Relationship to Clerkship Satisfaction.

Background And Objectives: The Accreditation Council for Graduate Medical Education and the Association of American Medical Colleges' commitment to competency-based medical education (CBME) has shifted the medical education landscape. Education methods conducive to CBME are learner-centered and give educators the opportunity to develop a more personalized approach to curricular development and delivery. By understanding learning preferences, educators are better positioned to respond to the changing needs of students.

Surgical window of opportunity trial reveals mechanisms of response and resistance to navtemadlin (KRT-232) in patients with recurrent glioblastoma.

Unlabelled: We investigated the effectiveness of navtemadlin (KRT-232) in treating recurrent glioblastoma. A surgical window-of-opportunity trial ( NCT03107780 ) was conducted on 21 patients to determine achievable drug concentrations within tumor tissue and examine mechanisms of response and resistance. Both 120 mg and 240 mg daily dosing achieved a pharmacodynamic impact.

Study protocol for measuring stigmatization in persistent tic disorders: development and validation of the Tourette discrimination-stigmatization scale.

Introduction: Persistent Tic Disorders such as Tourette Syndrome are common neurodevelopmental disorders that are highly stigmatized. Many individuals with Persistent Tic Disorders experience peer rejection, loneliness, and self-stigma. Experiencing stigmatization during childhood can influence the persistence of moderate-to-severe tics later in life.

A randomized controlled educational pilot trial of interictal epileptiform discharge identification for neurology residents.

Objective: To assess the effectiveness of an educational program leveraging technology-enhanced learning and retrieval practice to teach trainees how to correctly identify interictal epileptiform discharges (IEDs).

Methods: This was a bi-institutional prospective randomized controlled educational trial involving junior neurology residents. The intervention consisted of three video tutorials focused on the six IFCN criteria for IED identification and rating 500 candidate IEDs with instant feedback either on a web browser (intervention 1) or an iOS app (intervention 2).

A structured, journal-led peer-review mentoring program enhances peer review training.

Background: Peer review is essential to the advancement of knowledge. However, training on how to conduct peer review is limited, unorganized, and not well studied. Thus, we sought to determine if a structured mentored peer-review program improved peer review training as measured by multiple quantitative and qualitative assessments.

Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma.

Purpose: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600-mutated HGG.

Patients And Methods: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles.

Contributions of neuroimmune interactions to chemotherapy-induced peripheral neuropathy development and its prevention/therapy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating sequela that is difficult for both clinicians and cancer patients to manage. Precise mechanisms of CIPN remain elusive and current clinically prescribed therapies for CIPN have limited efficacy. Recent studies have begun investigating the interactions between the peripheral and central nervous systems and the immune system.

Expert accuracy and inter-rater agreement of "must-know" EEG findings for adult and child neurology residents.

Objective: We published a list of "must-know" routine EEG (rEEG) findings for trainees based on expert opinion. Here, we studied the accuracy and inter-rater agreement (IRA) of these "must-know" rEEG findings among international experts.

Methods: A previously validated online rEEG examination was disseminated to EEG experts.

Interest and Satisfaction of Telemedicine Use Among Ambulatory Neurology Patients in Western North Carolina During the COVID-19 Pandemic.

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