Metabolomics and network pharmacology approach to identify potential bioactive compounds from Trichoderma sp. against oral squamous cell carcinoma.

This study aimed to profile metabolites from five Trichoderma strains and assess their cytotoxic and pharmacological activities, particularly targeting oral squamous cell carcinoma (OSCC). UHPLC-TOF-MS analysis revealed the presence of 25 compounds, including heptelidic acid, viridiol isomers, and sorbicillinol from the different Trichoderma extracts. Pharmacokinetic analysis showed moderate permeability and low interaction with P-glycoprotein, suggesting good drug absorption with minimal interference in cellular uptake.

Assessing the Association Between Gadolinium-Based Contrast Agents and Parkinson Disease: Insights From the Korean National Health Insurance Service Database.

Objectives: This study aimed to investigate the association between the use of linear and macrocyclic gadolinium-based contrast agents (GBCAs) and the subsequent development of Parkinson disease (PD).

Methods: In this retrospective cohort study, data were extracted from the Korean National Health Insurance Service database, comprising 1,038,439 individuals. From this population, 175,125 adults aged 40 to 60 years with no history of brain disease were identified.

Incorporating Lymph Node Size at CT as an N1 Descriptor in Clinical N Staging for Lung Cancer.

Background The ninth edition of the TNM classification for lung cancer revised the N2 categorization, improving patient stratification, but prognostic heterogeneity remains for the N1 category. Purpose To define the optimal size cutoff for a bulky lymph node (LN) on CT scans and to evaluate the prognostic value of bulky LN in the clinical N staging of lung cancer. Materials and Methods This retrospective study analyzed patients who underwent lobectomy or pneumonectomy for lung cancer between January 2013 and December 2021, divided into development (2016-2021) and validation (2013-2015) cohorts.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Neither Bone Marrow Aspirate Concentrate nor Platelet-Rich Plasma Improves Patient-Reported Outcomes After Surgical Management of Acetabular Labral Tears; However, Bone Marrow Aspirate Concentrate May Be Effective for Moderate Cartilage Damage: A Systematic Review.

Purpose: To (1) systematically assess which orthobiologic agents are being used in acetabular labral repairs and (2) report all available outcomes for patients undergoing operative management for labral repairs with orthobiologic agents.

Methods: The PubMed, Embase, and Cochrane databases were queried in August 2023. Articles were included if they used an orthobiologic agent during hip arthroscopy for acetabular labral repair and reported functional outcomes.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure.

NaP-TRAP reveals the regulatory grammar in 5'UTR-mediated translation regulation during zebrafish development.

The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).

Use of equine H3N8 hemagglutinin as a broadly protective influenza vaccine immunogen.

Development of an efficacious universal influenza vaccines remains a long-sought goal. Current vaccines have shortfalls such as mid/low efficacy and needing yearly strain revisions to account for viral drift/shift. Horses undergo bi-annual vaccines for the H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many influenza strains.

Suite of Biochemical and Cell-Based Assays for the Characterization of Kirsten Rat Sarcoma (KRAS) Inhibitors and Degraders.

KRAS is an important oncogenic driver which is mutated in numerous cancers. Recent advances in the selective targeting of KRAS mutants via small molecule inhibitors and targeted protein degraders have generated an increase in research activity in this area in recent years. As such, there is a need for new assay platforms to profile next generation inhibitors which improve on the potency and selectivity of existing drug candidates, while evading the emergence of resistance.

Four-component protein nanocages designed by programmed symmetry breaking.

Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks.

scTrends: A living review of commercial single-cell and spatial 'omic technologies.

Understanding the rapidly evolving landscape of single-cell and spatial omic technologies is crucial for advancing biomedical research and drug development. We provide a living review of both mature and emerging commercial platforms, highlighting key methodologies and trends shaping the field. This review spans from foundational single-cell technologies such as microfluidics and plate-based methods to newer approaches like combinatorial indexing; on the spatial side, we consider next-generation sequencing and imaging-based spatial transcriptomics.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Development, deployment, and continuous monitoring of a machine learning model to predict respiratory failure in critically ill patients.

Objectives: This study describes the development and deployment of a machine learning (ML) model called Vent.io to predict mechanical ventilation (MV).

Materials And Methods: We trained Vent.

Features of hyperinflammation link the biology of Epstein-Barr virus infection and cytokine storm syndromes.

Background: Overt immune activation by viral infections can lead to cytokine storm syndromes, such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).

Objective: We aimed to compare the immune response to different viral pathogens to understand the connection between infections and cytokine storm syndromes.

Methods: We recruited children who sought care at the emergency department with fever for ≥3 days.

PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers composed of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of proliferator-activatedreceptor gamma coactivator 1-alpha (PGC-1α), a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNCs.

Nationwide, Couple-Based Genetic Carrier Screening.

Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

Device-Measured 24-Hour Movement Behaviors and Blood Pressure: A 6-Part Compositional Individual Participant Data Analysis in the ProPASS Consortium.

Background: Blood pressure (BP)-lowering effects of structured exercise are well-established. Effects of 24-hour movement behaviors captured in free-living settings have received less attention. This cross-sectional study investigated associations between a 24-hour behavior composition comprising 6 parts (sleeping, sedentary behavior, standing, slow walking, fast walking, and combined exercise-like activity [eg, running and cycling]) and systolic BP (SBP) and diastolic BP (DBP).

Innovations in Nuclear Medicine Imaging for Reactive Oxygen Species: Applications and Radiopharmaceuticals.

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review explores the potential of nuclear medicine imaging techniques for detecting ROS and evaluates various radiopharmaceuticals used in these applications.

Surgical Applications for Bone Marrow Aspirate Concentrate.

Bone marrow aspirate concentrate (BMAC) is an autologous orthobiologic agent that may be of benefit in specific surgical scenarios. Composed of elements isolated from bone marrow, including mesenchymal stromal cells, bone marrow-derived platelets, red and white blood cells, and hematopoietic precursors, BMAC has gained appeal for its potential to slow the progression of chondral degeneration, improve function, and provide symptomatic relief. BMAC is typically prepared during the final stages of a surgical procedure, beginning with bone marrow aspirate harvested from the iliac crest, distal femur, body of the ilium, or proximal humerus and then centrifuged to yield concentrated marrow cells.

Molecular and functional landscape of malignant serous effusions for precision oncology.

Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology.

High-throughput identification of repurposable neuroactive drugs with potent anti-glioblastoma activity.

Glioblastoma, the most aggressive primary brain cancer, has a dismal prognosis, yet systemic treatment is limited to DNA-alkylating chemotherapies. New therapeutic strategies may emerge from exploring neurodevelopmental and neurophysiological vulnerabilities of glioblastoma. To this end, we systematically screened repurposable neuroactive drugs in glioblastoma patient surgery material using a clinically concordant and single-cell resolved platform.