A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest.

Background: In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain.

Methods: We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed.

Analyzing sex imbalance in EGA and dbGaP biological databases: Recommendations for better practices.

Precision medicine aims at tailoring treatments to individual patient's characteristics. In this regard, recognizing the significance of sex and gender becomes indispensable for meeting the distinct healthcare needs of diverse populations. To this end, continuing a trend of improving data quality observed since 2014, the European Genome-phenome Archive (EGA) established a policy in 2018 that mandates data providers to declare the sex of donor samples, aiming to enhance data accuracy and prevent imbalance in sex classification.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases.

Standardized Data Elements for Patients With Acute Pulmonary Embolism: A Consensus Report From the Pulmonary Embolism Research Collaborative.

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment.

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells.

Despite recent advances in immunotherapies targeting single tumor-associated antigens, patients with multiple myeloma eventually relapse. ISB 2001 is a CD3 T cell engager (TCE) co-targeting BCMA and CD38 designed to improve cytotoxicity against multiple myeloma. Targeting of two tumor-associated antigens by a single TCE resulted in superior cytotoxic potency across a variable range of BCMA and CD38 tumor expression profiles mimicking natural tumor heterogeneity, improved resistance to competing soluble factors and exhibited superior cytotoxic potency on patient-derived samples and in mouse models.

Inorganic phosphate additives in meals and adaptations to 5-days of dietary inorganic phosphate loading alter acute calcium homeostasis in two randomized cross-over studies in healthy adults.

Diets containing inorganic phosphate additives are unbalanced with respect to calcium and these diets have been linked to the development of altered bone metabolism. Using 2 randomized cross-over studies in healthy humans, we (1) characterized the hormonal and urinary response to 2 meals with the same reported phosphorus amount (562-572 mg), where one was manufactured with inorganic phosphate additives and a comparatively lower Ca:P molar ratio (0.26 vs 0.

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.

Effect of Low-Dose Mulberry Fruit Extract on Postprandial Glucose and Insulin Responses: A Randomized Pilot Trial in Individuals with Type 2 Diabetes.

Adding mulberry fruit extract (MFE) to carbohydrate-rich meals can reduce postprandial glucose (PPG) and insulin (PPI) responses in healthy individuals. This pilot study assessed the acute postprandial effects of low doses of MFE in individuals with type 2 diabetes. In a randomized cross-over (within-subjects) design, 24 unmedicated adult males and females with type 2 diabetes (mean [SD] age 51.

Effect of Age and Sex on Anterior Cruciate Ligament Functional Tests Approximately 6 Months After Anterior Cruciate Ligament Reconstruction.

Purpose: To examine age- and sex-related differences in postoperative functional outcomes at approximately 6 months after anterior cruciate ligament reconstruction (ACLR).

Methods: In this study, patients who underwent primary ACLR performed a series of return-to-sport functional tests at 5 to 8 months after surgery. Functional tests included strength tests (knee extensors, knee flexors, hip abductors, and hip extensors), a balance test (Y-balance composite score), and hop tests (single, triple, crossover, and 6-m timed hop tests).

Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of . has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping.

Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors.

Background: Preclinical studies have demonstrated that VT1021, a first-in-class therapeutic agent, inhibits tumor growth via stimulation of thrombospondin-1 (TSP-1) and reprograms the tumor microenvironment. We recently reported data from the dose escalation part of a phase I study of VT1021 in solid tumors. Here, we report findings from the dose expansion phase of the same study.

Clinical, Neuroimaging, and Metabolic Footprint of the Neurodevelopmental Disorder Caused by Monoallelic Variants.

Background And Objectives: Hexokinase 1 (encoded by ) catalyzes the first step of glycolysis, the adenosine triphosphate-dependent phosphorylation of glucose to glucose-6-phosphate. Monoallelic variants causing a neurodevelopmental disorder (NDD) have been reported in 12 individuals.

Methods: We investigated clinical phenotypes, brain MRIs, and the CSF of 15 previously unpublished individuals with monoallelic variants and an NDD phenotype.

Modelling costs of interventional pulmonary embolism treatment: implications of US trends for a European healthcare system.

Aims: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the USA in the past decade, but the potential economic impact on European healthcare systems remains unknown.

Methods And Results: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the USA. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-20 and the model reflecting increasing access to advanced treatment from the PERT™ national quality assurance database registry 2018-21.

INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas.

Activating mutations in GNAQ/GNA11 occur in over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along with computational analyses of cancer dependency and gene expression datasets to identify the inositol-metabolizing phosphatase INPP5A as a selective dependency in GNAQ/11-mutant UM cells in vitro and in vivo. Mutant cells intrinsically produce high levels of the second messenger inositol 1,4,5 trisphosphate (IP3) that accumulate upon suppression of INPP5A, resulting in hyperactivation of IP3-receptor signaling, increased cytosolic calcium and p53-dependent apoptosis.