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.

Brain Care Score and Neuroimaging Markers of Brain Health in Asymptomatic Middle-Age Persons.

Objectives: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury.

Methods: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care.

Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias.

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

Background: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management.

Objective: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model.

An untapped window of opportunity for glioma: targeting therapy-induced senescence prior to recurrence.

High-grade gliomas are primary brain tumors that are incredibly refractory long-term to surgery and chemoradiation, with no proven durable salvage therapies for patients that have failed conventional treatments. Post-treatment, the latent glioma and its microenvironment are characterized by a senescent-like state of mitotic arrest and a senescence-associated secretory phenotype (SASP) induced by prior chemoradiation. Although senescence was once thought to be irreversible, recent evidence has demonstrated that cells may escape this state and re-enter the cell cycle, contributing to tumor recurrence.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Background: Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS.

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.

Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.

Retrospective value assessment of a dedicated, trauma hybrid operating room.

Background: In traumatic hemorrhage, hybrid operating rooms offer near simultaneous performance of endovascular and open techniques, with correlations to earlier hemorrhage control, fewer transfusions, and possible decreased mortality. However, hybrid operating rooms are resource intensive. This study quantifies and describes a single-center experience with the complications, cost-utility, and value of a dedicated trauma hybrid operating room.

SER-109: An Oral Investigational Microbiome Therapeutic for Patients with Recurrent Infection (rCDI).

Clostridioides difficile infection (CDI) is classified as an urgent health threat by the Centers for Disease Control and Prevention (CDC), and affects nearly 500,000 Americans annually. Approximately 20−25% of patients with a primary infection experience a recurrence, and the risk of recurrence increases with subsequent episodes to greater than 40%. The leading risk factor for CDI is broad-spectrum antibiotics, which leads to a loss of microbial diversity and impaired colonization resistance.

Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma.

There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas' molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions.

Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine).

Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa.

Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC).

Ileocolonic Histopathological and Microbial Alterations in the Irritable Bowel Syndrome: A Nested Community Case-Control Study.

Introduction: Histopathological alterations in the ileum and colon in irritable bowel syndrome (IBS) are controversial, and normal values are poorly established. We hypothesized that changes in mucosal immune cells characterize IBS and key changes in immune composition are associated with the mucosa-associated microbiota (MaM).

Methods: A nested case-control study (48 IBS and 106 controls included) from 745 colonoscopy participants in a random population sample.

Virtual Standardized Patient Simulation: Case Development and Pilot Application to High-Value Care.

Introduction: High-value care (HVC) suggests that good history taking and physical examination should lead to risk stratification that drives the use or withholding of diagnostic testing. This study describes the development of a series of virtual standardized patient (VSP) cases and provides preliminary evidence that supports their ability to provide experiential learning in HVC.

Methods: This pilot study used VSPs, or natural language processing-based patient avatars, within the USC Standard Patient platform.

The impact of standardized protocol implementation for surgical damage control and temporary abdominal closure after emergent laparotomy.

Background: To standardize care and promote early fascial closure among patients undergoing emergent laparotomy and temporary abdominal closure (TAC), we developed a protocol addressing patient selection, operative technique, resuscitation strategies, and critical care provisions. We hypothesized that primary fascial closure rates would increase following protocol implementation with no difference in complication rates.

Study Design: We performed a retrospective cohort analysis of 138 adult trauma and emergency general surgery patients who underwent emergent laparotomy and TAC, comparing protocol patients (n = 60) to recent historic controls (n = 78) who would have met protocol inclusion criteria.

Hypertonic saline resuscitation after emergent laparotomy and temporary abdominal closure.

Background: Our objective was to establish the safety of 3% hypertonic saline (HTS) resuscitation for trauma and acute care surgery patients undergoing emergent laparotomy and temporary abdominal closure (TAC) with the hypothesis that HTS administration would be associated with hyperosmolar hypercholoremic acidosis, lower resuscitation volumes, and higher fascial closure rates, without adversely affecting renal function.

Methods: We performed a retrospective cohort analysis of 189 trauma and acute care surgery patients who underwent emergent laparotomy and TAC, comparing patients with normal baseline renal function who received 3% HTS at 30 mL/h (n = 36) to patients with standard resuscitation (n = 153) by baseline characteristics, resuscitation parameters, and outcomes including primary fascial closure and Kidney Disease: Improving Global Outcomes stages of acute kidney injury.

Results: The HTS and standard resuscitation groups had similar baseline illness severity and organ dysfunction, though HTS patients had lower serum creatinine at initial laparotomy (1.

Neurologic involvement in patients with atypical Chediak-Higashi disease.

Objective: To delineate the developmental and progressive neurodegenerative features in 9 young adults with the atypical form of Chediak-Higashi disease (CHD) enrolled in a natural history study.

Methods: Patients with atypical clinical features, but diagnostically confirmed CHD by standard evaluation of blood smears and molecular genotyping, underwent complete neurologic evaluation, MRI of the brain, electrophysiologic examination, and neuropsychological testing. Fibroblasts were collected to investigate the cellular phenotype and correlation with the clinical presentation.

Neurologic involvement in patients with atypical Chediak-Higashi disease.

Objective: To delineate the developmental and progressive neurodegenerative features in 9 young adults with the atypical form of Chediak-Higashi disease (CHD) enrolled in a natural history study.

Methods: Patients with atypical clinical features, but diagnostically confirmed CHD by standard evaluation of blood smears and molecular genotyping, underwent complete neurologic evaluation, MRI of the brain, electrophysiologic examination, and neuropsychological testing. Fibroblasts were collected to investigate the cellular phenotype and correlation with the clinical presentation.

Leptin induces hippocampal synaptogenesis via CREB-regulated microRNA-132 suppression of p250GAP.

Leptin acts in the hippocampus to enhance cognition and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. Although leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) involved are not well understood.

Anticoagulation and survival in pulmonary arterial hypertension: results from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA).

Background: For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH).

Methods And Results: We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry.