Immunostimulatory/Immunodynamic model of mRNA-1273 to guide pediatric vaccine dose selection.

COVID-19 vaccines, including mRNA-1273, have been rapidly developed and deployed. Establishing the optimal dose is crucial for developing a safe and effective vaccine. Modeling and simulation have the potential to play a key role in guiding the selection and development of the vaccine dose.

Long-term safety and effectiveness of mRNA-1273 vaccine in adults: COVE trial open-label and booster phases.

Primary vaccination with mRNA-1273 (100-µg) was safe and efficacious at preventing coronavirus disease 2019 (COVID-19) in the previously reported, blinded Part A of the phase 3 Coronavirus Efficacy (COVE; NCT04470427) trial in adults (≥18 years) across 99 U.S. sites.

Individualized Machine-learning-based Clinical Assessment Recommendation System.

Background: Traditional clinical assessments often lack individualization, relying on standardized procedures that may not accommodate the diverse needs of patients, especially in early stages where personalized diagnosis could offer significant benefits. We aim to provide a machine-learning framework that addresses the individualized feature addition problem and enhances diagnostic accuracy for clinical assessments.

Methods: Individualized Clinical Assessment Recommendation System (iCARE) employs locally weighted logistic regression and Shapley Additive Explanations (SHAP) value analysis to tailor feature selection to individual patient characteristics.

CYpHER: Catalytic extracellular targeted protein degradation with high potency and durable effect.

Many disease-causing proteins have multiple pathogenic mechanisms, and conventional inhibitors struggle to reliably disrupt more than one. Targeted protein degradation (TPD) can eliminate the protein, and thus all its functions, by directing a cell's protein turnover machinery towards it. Two established strategies either engage catalytic E3 ligases or drive uptake towards the endolysosomal pathway.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

Background: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.

Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling.

Background: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project.

Methods: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled.

Amivantamab plus Chemotherapy in NSCLC with Exon 20 Insertions.

Background: Amivantamab has been approved for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor () exon 20 insertions who have had disease progression during or after platinum-based chemotherapy. Phase 1 data showed the safety and antitumor activity of amivantamab plus carboplatin-pemetrexed (chemotherapy). Additional data on this combination therapy are needed.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

Background: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown.

Methods: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart.

A Bivalent Omicron-Containing Booster Vaccine against Covid-19.

Background: The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known.

Methods: In this ongoing, phase 2-3 study, we compared the 50-μg bivalent vaccine mRNA-1273.

Antinucleocapsid Antibodies After SARS-CoV-2 Infection in the Blinded Phase of the Randomized, Placebo-Controlled mRNA-1273 COVID-19 Vaccine Efficacy Clinical Trial.

Background: Immunoassays for determining past SARS-CoV-2 infection have not been systematically evaluated in vaccinated persons in comparison with unvaccinated persons.

Objective: To evaluate antinucleocapsid antibody (anti-N Ab) seropositivity in mRNA-1273 (Moderna) vaccinees with breakthrough SARS-CoV-2 infection.

Design: Nested substudy of a phase 3 randomized, double-blind, placebo-controlled vaccine efficacy trial.

Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.

Background: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown.

Methods: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose.

Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of ICH. Incidence of hemorrhagic stroke has increased worldwide over the past 40 years, with shifts in the cause over time as hypertension management has improved and anticoagulant use has increased.

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.

Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.

Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection.

Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6-8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.

Morphologic Changes in the Lamina Cribrosa Upon Intraocular Pressure Lowering in Patients With Normal Tension Glaucoma.

Purpose: The purpose of this study was to investigate whether the lamina cribrosa (LC) curve changes in response to intraocular pressure (IOP) reduction following administration of topical ocular hypotensive eye drops in eyes with normal tension glaucoma (NTG).

Methods: Ninety-three eyes of 93 patients with treatment naïve NTG at initial examination and with ≥20% reduction from baseline IOP following administration of topical ocular hypotensive eye drops were included. Serial horizontal B-scan images of the optic nerve head (ONH) were obtained from each eye using enhanced depth imaging spectral domain optical coherence tomography (OCT) before and 1 year after IOP-lowering treatment.

Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents.

Background: The incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.

Methods: In this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart.