Molecular clustering on ctDNA improves the prognostic stratification of DLBCL patients compared to ctDNA levels.

Circulating tumor DNA (ctDNA) levels can help predict outcomes in diffuse large B-cell lymphoma (DLBCL), but its integration with DLBCL molecular clusters remains unexplored. Using the LymphGen tool in 77 DLBCL with both ctDNA and tissue biopsy, a 95.8% concordance rate in molecular cluster assignment was observed, showing the reproducibility of molecular clustering on ctDNA.

Consensus and guidelines on diagnosis and management of polypoidal choroidal vasculopathy (PCV) from the Asia-Pacific Vitreo-retina Society (APVRS).

A panel of 21 international experts are formed by the Asia-Pacific Vitreo-retina Society to work out the consensus and guidelines on polypoidal choroidal vasculopathy (PCV). PCV is a common subtype of neovascular age-related macular degeneration and is more prevalent in Asian populations. Recent advancement in imaging technology allows greater understanding of the disease process of PCV.

Decreased opioid receptor availability and impaired neurometabolic coupling as signatures of morphine tolerance in male rats: A positron emission tomography study.

Translational neuroimaging techniques are needed to address the impact of opioid tolerance on brain function and quantitatively monitor the impaired neuropharmacological response to opioids at the CNS level. A multiparametric PET study was conducted in rats. Rats received morphine daily to induce tolerance (15 mg/kg/day for 5 days), followed by 2-day withdrawal.

CO Adsorption on a Single-Atom Catalyst Stably Embedded in Graphene.

Confined single metal atoms in graphene-based materials have proven to be excellent catalysts for several reactions and promising gas sensing systems. However, whether the chemical activity arises from the specific type of metal atom or is a direct consequence of the confinement itself remains unclear.

The thyroid hormone activating enzyme, DIO2, is a potential pan-cancer biomarker and immunotherapy target.

Purpose: Type 2 deiodinase (D2), encoded by DIO2 gene, catalyzes the activation of the prohormone thyroxine (T4) into the bioactive hormone triiodothyronine (T3) in peripheral tissues, thereby regulating the intracellular Thyroid Hormone (TH) availability. Recently, several studies have demonstrated that a drastic increase in the peripheral activation of TH, via D2, fosters tumor progression, metastasis, and immunity.

Methods: To further prove the clinical relevance of D2 in human cancer, based on public Database of The Cancer Genome Atlas (TCGA), we conducted a pan-cancer analysis of DIO2 expression in various cancer types and investigated the association of DIO2 expression with the tumor microenvironment (TME) components and immune cell infiltration, along with the DIO2 genetic alteration types.

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8 T-cell infiltration while reducing neutrophils.

High-resolution X-ray phase-contrast tomography of human placenta with different wavefront markers.

Phase-contrast micro-tomography ([Formula: see text]CT) with synchrotron radiation can aid in the differentiation of subtle density variations in weakly absorbing soft tissue specimens. Modulation-based imaging (MBI) extracts phase information from the distortion of reference patterns, generated by periodic or randomly structured wavefront markers (e.g.

ECM Modifications Driven by Age and Metabolic Stress Directly Promote the Vascular Smooth Muscle Cell Osteogenic Processes.

Background: The ECM (extracellular matrix) provides the microenvironmental niche sensed by resident vascular smooth muscle cells (VSMCs). Aging and disease are associated with dramatic changes in ECM composition and properties; however, their impact on the VSMC phenotype remains poorly studied.

Methods: Here, we describe a novel in vitro model system that utilizes endogenous ECM to study how modifications associated with age and metabolic disease impact the VSMC phenotype.

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2.

The SARS-CoV-2 papain-like protease PLpro has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its ability to antagonize the host immune response. Targeting the PLpro function is recognized as a promising mechanism to modulate viral replication, while supporting host immune responses. However, the development of PLpro-specific inhibitors remains challenging.

Combination of Broad Light-Absorption CuS with S,C,N-TiO: Assessment of Photocatalytic Performance in Nitrogen Fixation Reaction.

In the field of solar energy storage, photocatalytic ammonia production is a next-generation technology. The rapid recombination of charges and insignificant utilization of the sunlight spectrum are bottlenecks of effective photocatalytic N fixation. The introduction of impurities in the crystal lattice and the development of heterojunctions could effectively segregate carriers and improve the solar-light-harvesting capability, which can boost NH generation.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Bilateral hip exoskeleton assistance enables faster walking in individuals with chronic stroke-related gait impairments.

Millions of individuals surviving a stroke have lifelong gait impairments that reduce their personal independence and quality of life. Reduced walking speed is one of the major problems limiting community mobility and reintegration. Previous studies have shown positive effect of robot-assisted gait training utilizing hip exoskeletons for individuals with gait impairments due to a stroke, leading to increased walking speed in post-treatment compared to pre-treatment assessments.

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Deep Learning Radiomics Nomogram Based on MRI for Differentiating between Borderline Ovarian Tumors and Stage I Ovarian Cancer: A Multicenter Study.

Rationale And Objectives: To develop and validate a deep learning radiomics nomogram (DLRN) based on T2-weighted MRI to distinguish between borderline ovarian tumors (BOTs) and stage I epithelial ovarian cancer (EOC) preoperatively.

Materials And Methods: This retrospective multicenter study enrolled 279 patients from three centers, divided into a training set (n = 207) and an external test set (n = 72). The intra- and peritumoral radiomics analysis was employed to develop a combined radiomics model.

Bond strength to eroded dentin as per chlorhexidine use for controlling erosive wear or interface aging: an 18-month assay.

The aim of this study was to assess the effect of a chlorhexidine digluconate solution (CHX) applied as an antiproteolytic agent for controlling erosive tooth wear or as part of the adhesive treatment on long-term bond strength to eroded dentin. Dentin specimens were abraded with a 600-grit silicon carbide (SiC) paper for 1 min (sound dentin - S), subsequently treated with 2% CHX for 1 min (with excess removed, followed by a 6-hour rest), and eroded by exposure to Coca-Cola for 5 min, three times a day, for 5 days (CHX-treated and eroded dentin - CHXE), or only eroded (eroded dentin - E). The specimens were acid-etched (15 s), rinsed (30 s), dried (15 s), and rehydrated with 1.

Interventions to Reduce Mental Health Stigma in Young People: A Systematic Review and Meta-Analysis.

Importance: Mental health stigma is a considerable barrier to help-seeking among young people.

Objective: To systematically review and meta-analyze randomized clinical trials (RCTs) of interventions aimed at reducing mental health stigma in young people.

Data Sources: Comprehensive searches were conducted in the CENTRAL, CINAHL, Embase, PubMed, and PsycINFO databases from inception to February 27, 2024.

Cardiovascular diseases, prevention and management of complications in older adults and frail patients treated for elective or post-traumatic hip orthopaedic interventions.

Due to the aging population, focusing on healthy aging has become a global priority. Cardiovascular diseases (CVDs) and frailty, characterized by increased vulnerability to adverse stress and health events, interact synergistically in advanced age. In older adults, hip fractures are a frequent dramatic "life-transition" event.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Gene therapy in hemophilia: the dawn of a new era.

Hemophilia A and B are hereditary bleeding disorders associated with the X chromosome, stemming from genetic defects in the coding of coagulation factor (F)VIII or FIX protein, leading to partial or complete deficiency. In the absence of effective prophylaxis, these deficiencies can result in irreversible joint damage, known as hemophilic arthropathy, and subsequent disability. Despite advancements in hemophilia treatment, individuals with severe forms of the disease continue to face a high risk of bleeding, particularly in instances of trauma or major surgical procedures.

Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Prilling of crystallizable water-in-oil emulsions: Towards co-encapsulation of hydrophilic and lipophilic active ingredients within lipid microparticles.

Multiparticulate drug delivery systems offer advantages in controlled release, dose flexibility, and personalized medicine. Fusion prilling, a process that produces spherical lipid-based microparticles through vibrating nozzles, is gaining interest in the field. This study aims to explore the use of fusion prilling to encapsulate crystallizable water-in-oil emulsions, enabling the incorporation of hydrophilic active pharmaceutical ingredients (APIs) within lipid matrices.

Toward curing neurological autoimmune disorders: Biomarkers, immunological mechanisms, and therapeutic targets.

Autoimmune neurology is a rapidly expanding field driven by the discovery of neuroglial autoantibodies and encompassing a myriad of conditions affecting every level of the nervous system. Traditionally, autoantibodies targeting intracellular antigens are considered markers of T cell-mediated cytotoxicity, while those targeting extracellular antigens are viewed as pathogenic drivers of disease. However, recent advances highlight complex interactions between these immune mechanisms, suggesting a continuum of immunopathogenesis.

Effect of fezolinetant on patient-reported quality-of-life outcomes: Data from a phase 3b study (DAYLIGHT) of the treatment of moderate to severe vasomotor symptoms associated with menopause in women considered unsuitable for hormone therapy.

Objective: To report patient-reported quality-of-life (QOL) outcomes in the DAYLIGHT study.

Study Design: DAYLIGHT was a phase 3b, randomized, double-blind, 24-week, placebo-controlled study. Participants were women aged ≥40 to ≤65 years with moderate to severe vasomotor symptoms (VMS) considered unsuitable for hormone therapy (HT) (contraindications, caution, stoppers, or averse) randomized 1:1 to placebo or fezolinetant 45 mg once daily.

A Machine Learning Model Using Cardiac CT and MRI Data Predicts Cardiovascular Events in Obstructive Coronary Artery Disease.

Background Multimodality imaging is essential for personalized prognostic stratification in suspected coronary artery disease (CAD). Machine learning (ML) methods can help address this complexity by incorporating a broader spectrum of variables. Purpose To investigate the performance of an ML model that uses both stress cardiac MRI and coronary CT angiography (CCTA) data to predict major adverse cardiovascular events (MACE) in patients with newly diagnosed CAD.