First-generation and preclinical evaluation of an EphA5-targeted antibody-drug conjugate in solid tumors.

Contemporary cancer treatment strategies are shifting toward targeted therapies to improve efficacy and minimize toxicity. Here, we report the design and preclinical evaluation of MBRC-101, a first-in-class antibody-drug conjugate (ADC) targeting EphA5, a receptor tyrosine kinase with an established role in embryonic development but not extensively studied in cancer. We show that EphA5 is expressed in multiple solid tumors, including cancers of the aerodigestive (non-small cell lung, head and neck, gastric, colon, and pancreatic) and genitourinary (bladder and ovary) tracts, as well as most breast cancer subsets (including triple-negative tumors), with limited expression in normal tissues.

Human protein interactome structure prediction at scale with Boltz-2.

In humans, protein-protein interactions mediate numerous biological processes and are central to both normal physiology and disease. Extensive research efforts have aimed to elucidate the human protein interactome, and comprehensive databases now catalog these interactions at scale. However, structural coverage of the human protein interactome is limited and remains challenging to resolve through experimental methodology alone.

Conformational ligand-directed targeting of calcium-dependent receptors in acute trauma.

Background: Trauma is a leading cause of mortality, but injury-specific molecular targets remain largely unknown. We hypothesized that distinctive yet unrecognized tissue targets accessible to circulating ligands might emerge during trauma, thereby underscoring a trauma-related proteome.

Methods: We screened a peptide library to discover targets in a porcine model of major trauma: compound femur fracture with hemorrhagic shock.

The Co-Pilot Project in wartime: lessons from Lviv, Ukraine.

Objective: The ongoing war in Ukraine has introduced many challenges to an already overburdened and resource-limited medical system. Longitudinal collaborations, material support, educational outreach, and surgical mentorship are essential for improving outcomes and standards of neurosurgical care in extreme settings such as in times of war.

Methods: Operating in Ukraine since 2016 through the coordination of Razom, the Co-Pilot Project has organized multiple United States-based mission trips to Ukraine to support local physicians during wartime, including a trip between April and May of 2023.

Brain-derived textiloma post glioblastoma resection and application of oxidized regenerated cellulose: A pilot, bedside-to-bench, translational study.

Oxidized regenerated cellulose (ORC; marketed as Surgicel® and Tabotamp®) is routinely used as an intraoperative hemostatic agent. Rarely, residual ORC has been associated with a foreign body reaction generating cystic or granulomatous lesions (i.e.

High-throughput prediction of peptide structural conformations with AlphaFold2.

Protein structure prediction artificial intelligence/machine learning (AI/ML) approaches has sparked substantial research interest in structural biology and adjacent disciplines. More recently, AlphaFold2 (AF2) has been adapted for the prediction of multiple structural conformations-beyond the original scope of predicting single-state structures. This is accomplished by using multiple random seeds and subsampling the multiple sequence alignment (MSA).

Generative artificial intelligence performs rudimentary structural biology modeling.

Natural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling.

Generative artificial intelligence performs rudimentary structural biology modeling.

Natural language-based generative artificial intelligence (AI) has become increasingly prevalent in scientific research. Intriguingly, capabilities of generative pre-trained transformer (GPT) language models beyond the scope of natural language tasks have recently been identified. Here we explored how GPT-4 might be able to perform rudimentary structural biology modeling.

Modeling of ACE2 and antibodies bound to SARS-CoV-2 provides insights into infectivity and immune evasion.

Given the COVID-19 pandemic, there is interest in understanding ligand-receptor features and targeted antibody-binding attributes against emerging SARS-CoV-2 variants. Here, we developed a large-scale structure-based pipeline for analysis of protein-protein interactions regulating SARS-CoV-2 immune evasion. First, we generated computed structural models of the Spike protein of 3 SARS-CoV-2 variants (B.

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection.

While the development of different vaccines slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections has continued to fuel the COVID-19 pandemic. To secure at least partial protection in the majority of the population through 1 dose of a COVID-19 vaccine, delayed administration of boosters has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may induce breakthrough infections due to intermittent lapses in protection.

Self-efficacy and knowledge in pediatrics among family medicine physicians in Armenia: A survey study.

Background: Armenia has trained physicians to practice family medicine (FM) for over 20 years. The pediatric population comprises a significant proportion of patients seen by FM practices, yet to date, there have been no studies assessing the knowledge and self-efficacy of FM physicians regarding pediatric care. As the first step is needs assessment to improve the quality of care, this study aims to assess the self-efficacy and knowledge of FM physicians regarding the care of pediatric patients.

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection.

While the development of different vaccines has slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections continues to fuel the pandemic. As a strategy to secure at least partial protection, with a single dose of a given COVID-19 vaccine to maximum possible fraction of the population, administration of subsequent doses (or boosters) has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may jeopardize the attainment of herd immunity due to intermittent lapses in protection.

Gross Total Resection of a Ruptured Micro-arteriovenous Malformation within the Cerebellar Peduncle: A Case Report and Qualitative Review of the Literature.

Deep-seated micro-arteriovenous malformations (micro-AVMs) may pose a challenge for complete yet safe resection. We propose the strategic placement of two to three microaneurysm clips throughout the hemorrhage cavity to successfully localize the micro-AVM nidus via digital subtraction angiography (DSA). We successfully demonstrate this novel method in a 15-year-old adolescent boy with cerebellar intraparenchymal hemorrhage who underwent hematoma evacuation and expansile duraplasty.

Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection.

Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662-C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662-C671 epitope were performed.

Corpus Callosotomy in the Modern Era: Origins, Efficacy, Technical Variations, Complications, and Indications.

Corpus callosotomy is among the oldest surgeries performed for drug-resistant epilepsy. Since it was first performed in 1940, numerous studies have assessed its outcomes in various patient populations in addition to describing different extents of sectioning and emerging technologies (i.e.

Structural models of SARS-CoV-2 Omicron variant in complex with ACE2 receptor or antibodies suggest altered binding interfaces.

There is enormous ongoing interest in characterizing the binding properties of the SARS-CoV-2 Omicron Variant of Concern (VOC) (B.1.1.

Underutilization of advanced presurgical studies and high rates of vagus nerve stimulation for drug-resistant epilepsy: a single-center experience and recommendations.

Introduction: Epilepsy surgery continues to be profoundly underutilized despite its safety and effectiveness. We sought to investigate factors that may contribute to this phenomenon, with a particular focus on the antecedent underutilization of appropriate preoperative studies.

Methods: We reviewed patient data from a pediatric epilepsy clinic over an 18-month period.

Apropos of Universal Epitope Discovery for COVID-19 Vaccines: A Framework for Targeted Phage Display-Based Delivery and Integration of New Evaluation Tools.

Targeted bacteriophage (phage) particles are potentially attractive yet inexpensive platforms for immunization. Herein, we describe targeted phage capsid display of an immunogenically relevant epitope of the SARS-CoV-2 Spike protein that is empirically conserved, likely due to the high mutational cost among all variants identified to date. This observation may herald an approach to developing vaccine candidates for broad-spectrum, towards universal, protection against multiple emergent variants of coronavirus that cause COVID-19.

Completion Posterior Quadrant Disconnection After Failed Temporal Lobectomy: 2-Dimensional Operative Video.

Epilepsy is a chronic seizure disorder that affects about 1% of the global population.1 When seizure freedom cannot be obtained solely through antiseizure medicines (ASMs), the condition is termed medically refractory epilepsy (MRE).2,3 Though posterior quadrant disconnection (PQD) is underutilized in our experience, it is a highly effective surgical procedure for MRE restricted to the temporal, parietal, and/or occipital lobes.