Efficacy of ursodeoxycholic acid for bile reflux after distal gastrectomy in patients with gastric cancer: A secondary analysis of the PEGASUS-D randomized clinical trial.

Background: Few studies have been conducted on the prevention of bile reflux in gastric cancer patients who have undergone gastrectomy. The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing bile reflux after gastrectomy in patients with gastric cancer.

Methods: This study was a secondary analysis of the PEGASUS-D trial, a randomized, double-blind, placebo-controlled clinical trial.

Fractal analysis of left ventricular trabeculae in heart failure with preserved ejection fraction patients with multivessel coronary artery disease.

Objectives: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD).

Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.

Purpose: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors.

Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Inhibition of catechol-O-methyltransferase (COMT) by heparin oligosaccharides with specific structures.

COMT inhibitors are commonly used to improve the effectiveness of levodopa in treating Parkinson's disease by inhibiting its conversion to 3-O-methyldopa. Because of the serious side effect of nitrocatechol COMT inhibitors, it is necessary to develop non-nitrocatechol COMT inhibitors with a higher safety profile. Heparin has been observed to bind to COMT.

Experiment on Compressive Properties and Microscopic Analysis of Sea Sand Geopolymer-Based Recycled Concrete.

For marine and coastal engineering, construction resources have become scarce due to a limited local supply. Sea sand geopolymer-based recycled concrete (SSGRC) is an innovative cementitious material known for its eco-friendly benefits and corrosion resistance. This study explores the mechanical properties of SSGRC.

Serum Exosome-Derived microRNA-193a-5p and miR-381-3p Regulate Adenosine 5'-Monophosphate-Activated Protein Kinase/Transforming Growth Factor Beta/Smad2/3 Signaling Pathway and Promote Fibrogenesis.

Introduction: Liver fibrosis results from chronic liver injury and inflammation, often leading to cirrhosis, liver failure, portal hypertension, and hepatocellular carcinoma. Progress has been made in understanding the molecular mechanisms underlying hepatic fibrosis; however, translating this knowledge into effective therapies for disease regression remains a challenge, with considerably few interventions having entered clinical validation. The roles of exosomes during fibrogenesis and their potential as a therapeutic approach for reversing fibrosis have gained significant interest.

The Inflammasome-Dependent Dysfunction and Death of Retinal Ganglion Cells after Repetitive Intraocular Pressure Spikes.

The dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies, where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of a similar intensity and duration failed to induce pathology.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

SARS-CoV-2 infection establishes a stable and age-independent CD8 T cell response against a dominant nucleocapsid epitope using restricted T cell receptors.

The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8 T cells play a vital role. Nonetheless, the characterization of the specificity and TCR composition of CD8 T cells targeting non-spike protein of SARS-CoV-2 before and after infection remains incomplete. Here, we analyzed CD8 T cells recognizing six epitopes from the SARS-CoV-2 nucleocapsid (N) protein and found that SARS-CoV-2 infection slightly increased the frequencies of N-recognizing CD8 T cells but significantly enhanced activation-induced proliferation compared to that of the uninfected donors.

Transgenic viral expression of PH-20, IL-12, and sPD1-Fc enhances immune cell infiltration and anti-tumor efficacy of an oncolytic virus.

Oncolytic viruses are of significant clinical interest due to their ability to directly infect and kill tumors and enhance the anti-tumor immune response. Previously, we developed KLS-3010, a novel oncolytic virus derived from the International Health Department-White (IHD-W) strain vaccinia virus, which has robust tumoricidal effects. In the present study, we generated a recombinant oncolytic virus, KLS-3020, by inserting three transgenes (hyaluronidase [PH-20], interleukin-12 [IL-12], and soluble programmed cell death 1 fused to the Fc domain [sPD1-Fc]) into KLS-3010 and investigated its anti-tumor efficacy and ability to induce anti-tumor immune responses in CT26.

Anti-Cancer Roles of Probiotic-Derived P8 Protein in Colorectal Cancer Cell Line DLD-1.

A novel probiotics-derived protein, P8, suppresses the growth of colorectal cancer (CRC). P8 can penetrate the cell membrane via endocytosis and cause cell cycle arrest in DLD-1 cells through down-regulation of CDK1/Cyclin B1. However, neither the protein involved in the endocytosis of P8 nor the cell cycle arrest targets of P8 are known.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

Background And Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance.

Predictive Value of KLASS-02-QC Assessment Score on KLASS-02 Surgical Outcomes: Validation of Surgeon Quality Control and Standardization for D2 Lymphadenectomy.

Objective: The aim of this study was to audit the 22 items and assessed each item's predictive value on surgical outcomes.

Background: The KLASS-02 trial revealed that the oncologic outcomes of laparoscopic distal gastrectomy are not inferior to open distal gastrectomy in patients with advanced gastric cancer. The surgeons participating in this trial were chosen based on the assessment scores from the KLASS-02-QC trial, which used 22 items for standardization of D2 lymphadenectomy and quality control.

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

Background And Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC.

Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.

Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles.

Photodissociation of HS: A New Pathway for the Production of Vibrationally Excited Molecular Hydrogen in the Interstellar Medium.

Hydrogen sulfide (HS) is the most abundant S-bearing molecule in the solar nebula. Although its photochemistry has been studied for decades, the H fragment channel is still not well-understood. Herein, we describe the photodissociation dynamics of HS + → S(S) + H(XΣ) with the excitation wavelength of 122 nm ≤ λ ≤ 136 nm.

Modeling the Effect of Alternative Cementitious Binders in Ultra-High-Performance Concrete.

The use of alternative cementitious binders is necessary for producing sustainable concrete. Herein, we study the effect of using alternative cementitious binders in ultra-high-performance concrete (UPHC) by calculating the phase assemblages of UHPC in which Portland cement is replaced with calcium aluminate cement, calcium sulfoaluminate cement, metakaolin or blast furnace slag. The calculation result shows that replacing Portland cement with calcium aluminate cement or calcium sulfoaluminate cement reduces the volume of C-S-H but increases the overall solid volume due to the formation of other phases, such as strätlingite or ettringite.

Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.

Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC). The extracellular matrix (ECM) contributes to immune exclusion. However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.