Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer.

Objective: We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.

Methods: Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.

Using a 'Students as Partners' model to develop an authentic assessment promoting employability skills in undergraduate life science education.

Authentic assessments (AA) include three principles, realism, cognitive challenge, and evaluative judgment, and replicate professional workplace expectations. Developing AA in undergraduate life science education is necessary to promote critical skill development and adequately prepare students for the workplace. Using a 'Students-as-Partners' (SAP) approach, five students, an educational developer and the instructor codeveloped an AA requiring students to utilize scientific literacy (SL) and critical thinking (CT) skills to develop a data extraction table and generate communication outputs for scientific and nonscientific audiences.

Nuclear Medicine Cerebral Perfusion Studies as an Ancillary Test to Support Evaluation of Brain Death/Death by Neurologic Criteria: Single-Center Experience in Infants, 2005-2022.

Objective: To describe the use of nuclear medicine cerebral perfusion studies as an ancillary test for brain death/death by neurologic criteria (BD/DNC) in infants aged under 1 year.

Design: Retrospective case series.

Setting: Single-center, quaternary, academic children's hospital in the United States.

Mucosal SARS-CoV-2 S1 adenovirus-based vaccine elicits robust systemic and mucosal immunity and protects against disease in animals.

Unlabelled: The COVID-19 pandemic has emphasized the importance and need for accessible safe, effective, and versatile vaccine platforms. While approved SARS-CoV-2 vaccines have been instrumental in saving lives and reducing healthcare and economic burdens, the induction of mucosal immunity remains an unmet need. Here, we engineered and evaluated a non-replicating adenovirus 5 (rAd5)-based vaccine expressing the SARS-CoV-2 S1 subunit (rAd5-SARS2-S1).

-6-methyladenosine (m6A) promotes the nuclear retention of mRNAs with intact 5' splice site motifs.

In humans, misprocessed mRNAs containing intact 5' Splice Site (5'SS) motifs are nuclear retained and targeted for decay by ZFC3H1, a component of the Poly(A) Exosome Targeting complex, and U1-70K, a component of the U1 snRNP. In , the ZFC3H1 homolog, Red1, binds to the YTH domain-containing protein Mmi1 and targets certain RNA transcripts to nuclear foci for nuclear retention and decay. Here we show that YTHDC1 and YTHDC2, two YTH domain-containing proteins that bind to -6-methyladenosine (m6A) modified RNAs, interact with ZFC3H1 and U1-70K, and are required for the nuclear retention of mRNAs with intact 5'SS motifs.

LI-RADS US Surveillance Version 2024 for Surveillance of Hepatocellular Carcinoma: An Update to the American College of Radiology US LI-RADS.

In 2017, the American College of Radiology introduced the US Liver Imaging Reporting and Data System (LI-RADS) as a framework for US surveillance of patients at risk for developing hepatocellular carcinoma. This has aided in the standardization of technique, clinical reporting, patient management, data collection, and research. Emerging evidence has helped inform changes to the algorithm, now released as LI-RADS US Surveillance version 2024.

Oxidative Deformylation of the Predominant DNA Lesion 5-Formyl-2'-deoxyuridine.

Radical oxidation of DNA gives rise to potentially deleterious lesions such as strand breaks and various nucleobase modifications including 5-formyl-2'-deoxyuridine (5-fo-dU), a prevalent product derived from the oxidation of the C5-methyl group of thymidine. The present study investigates the unusual transformation of 5-fo-dU into 5-hydroxy-2'-deoxyuridine (5-oh-dU) and 5,6-dihydroxy-5,6-dihydro-2'-deoxuridine (gly-dU), two products typically associated with the oxidation of 2'-deoxycytidine. Detailed mechanistic analyses reveal that hydrogen peroxide, either generated as a byproduct of ascorbate autoxidation or added exogenously, mediates the formation of these oxidatively induced C5-dealkylated products.

Altered sphingolipid profile in response to skeletal muscle injury in a mouse model of type 1 diabetes mellitus.

A complication of type 1 diabetes mellitus (T1DM) is diabetic myopathy that includes reduced regenerative capacity of skeletal muscle. Sphingolipids are a diverse family of lipids with roles in skeletal muscle regeneration. Some studies have found changes in sphingolipid species levels in T1DM, however, the effect of T1DM on a sphingolipid panel in regenerating skeletal muscle has not been examined.

The AMPK allosteric activator MK-8722 improves the histology and spliceopathy in myotonic dystrophy type 1 (DM1) skeletal muscle.

Multiple signaling pathways have been reported to be altered in Myotonic Dystrophy type 1 (DM1) skeletal muscle, contributing to pathogenicity. In particular, previous work established that AMPK signaling, a key sensor of energy metabolism, is repressed in DM1 mouse muscle and that activating AMPK through exercise and/or with pharmacological activators is beneficial for the DM1 muscle phenotype. Here, we explored the effects of a newer, more specific allosteric AMPK activator acting directly on AMPK.

Autoimmune hepatitis: Towards a personalized treatment.

Autoimmune hepatitis is an uncommon condition that affects both adults and children and is characterized by chronic and recurrent inflammatory activity in the liver. This inflammation is accompanied by elevated IgG and autoantibody levels. Historically, treatment consists of steroids with the addition of azathioprine, which results in remission in approximately 80% of patients.

Serological Markers as Predictors of Anti-TNF Response in Children with Crohn's Disease.

Background: To advance personalized medicine in pediatric Crohn's disease (CD), we aimed to explore the utility of serological biomarkers in predicting response to anti-tumor necrosis factor (TNF).

Methods: Children with CD were enrolled at initiation of anti-TNF and followed prospectively at 4 and 12 months thereafter, as well as at last follow-up. At baseline, 10 serological markers of the "PROMETHEUS® IBD sgi Diagnostic test" were measured, including pANCA, ASCA IgG and IgA, anti-CBir1, anti-OmpC, anti-A4-Fla2, anti-Fla-X, SAA, ICAM-1 and VCAM-1.

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved.

Changing expectations toward end-of-life communication: An experimental investigation.

Objectives: To investigate the effect of a) a brief video intervention and b) end-of-life (EOL) conversations with relatives on EOL communication expectations.

Methods: 272 participants from the general population were randomly assigned to three different video conditions (Intervention group: Persons reporting positive EOL conversation experiences +imagination task, Control group 1: Video unrelated to EOL topics, Control group 2: Persons reporting different attitudes toward EOL conversations +imagination task). Primary outcome was negative expectations.

Benefits of Clinical Decision Support Systems for the Management of Noncommunicable Chronic Diseases: Targeted Literature Review.

Background: Clinical decision support systems (CDSSs) are designed to assist in health care delivery by supporting medical practice with clinical knowledge, patient information, and other relevant types of health information. CDSSs are integral parts of health care technologies assisting in disease management, including diagnosis, treatment, and monitoring. While electronic medical records (EMRs) serve as data repositories, CDSSs are used to assist clinicians in providing personalized, context-specific recommendations derived by comparing individual patient data to evidence-based guidelines.

Adult Phenotype of -Associated Disorders.

Background And Objectives: Pathogenic variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with variants.

Movement Behaviors and Bone Biomarkers in Young Pediatric Cancer Survivors: A Cross-Sectional Analysis of the iBoneFIT Project.

Background/objectives: This study aims to investigate the association of movement behaviors with irisin, sclerostin, and bone turnover markers in young pediatric cancer survivors.

Methods: A total of 116 young pediatric cancer survivors (12.1 ± 3.

Comparison of the Minimum Inhibitory and Mutant Prevention Drug Concentrations for Pradofloxacin and 7 Other Antimicrobial Agents Tested Against Swine Isolates of and .

Pradofloxacin is a dual targeting, bactericidal fluoroquinolone recently approved for treating bacteria causing swine respiratory disease. Currently, an abundance of in vitro data does not exist for pradofloxacin. We determined the minimum inhibitory concentration (MIC) and mutant prevention concentrations (MPC) of pradofloxacin compared to ceftiofur, enrofloxacin, florfenicol, marbofloxacin, tildipirosin, tilmicosin and tulathromycin against swine isolates of and .

Wound Gel Formulations Containing Poloxamer 407 and Polyhexanide Have Antimicrobial and Antibiofilm Activity Against Wound-Associated Microbial Pathogens.

Chronic wounds are often caused or exacerbated by microbial biofilms that are highly resistant to antimicrobial treatments and that prevent healing. This study compared the antimicrobial and antibiofilm activity of nine topical wound treatments, comprising gels with different concentrations of poloxamer 407 (20-26%) and different pH levels (4-6) and containing polyhexanide (PHMB) as an antimicrobial agent; the effects of pH on wound gels containing this agent have not been previously reported. The wound gel formulations were tested against six common wound-associated microbial pathogens: , , , , , and .