LDL-Cholesterol Lowering Agents (Statins and PCSK9 Inhibitors) and the Risk of Intracerebral Hemorrhage: A Network Meta-Analysis.

Background And Purpose: Statin therapy reduces the risk of ischemic stroke; however, certain studies have observed an increased incidence of intracerebral hemorrhage (ICH). Moreover, proprotein convertase subtilisin/kexin type 9(PCSK-9) inhibitors have emerged as a powerful class of lipid-lowering medications, potentially with a lower propensity for causing hemorrhagic events. To investigate this matter further, we conducted a network meta-analysis of randomized controlled trials (RCTs) involving statins and PCSK-9 inhibitors that reported occurrences of ICH.

Ethylene glycol toxicosis in 39 sport horses following ingestion of contaminated water: a case report.

Ethylene glycol toxicosis is a common occurrence in dogs and cats but has been reported in other species as well. Up to date, only one case of ethylene glycol toxicosis has been described in horses, and specific guidelines for treating ethylene glycol intoxication in this species are not available. Here we describe the case of 39 sport horses that ingested water contaminated with ethylene glycol.

With Proper Surgical Indications, Sex-Based Differences in Pathology Do Not Impact Hip Arthroscopy Outcomes or Complications: A Systematic Review.

Purpose: To identify sex-based differences in pathology, outcomes, and complications after hip arthroscopy for femoroacetabular impingement (FAI), and to compare patient-reported outcomes (PRO) scores between males and females.

Methods: The PubMed and MEDLINE databases were searched in September 2024, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies had data stratified by sex, minimum 2-year patient reported outcome (PRO) scores for hip arthroscopy in the setting of FAI and labral pathology, and a 2014 or later publication date.

Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.

Drug repositioning for Parkinson's disease: an emphasis on artificial intelligence approaches.

Parkinson's disease (PD) is one of the most incapacitating neurodegenerative diseases (NDDs). PD is the second most common NDD worldwide which affects approximately 1 to 2 percent of people over 65 years. It is an attractive pursuit for artificial intelligence (AI) to contribute to and evolve PD treatments through drug repositioning by repurposing existing drugs, shelved drugs, or even candidates that do not meet the criteria for clinical trials.

Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

A Prospective Phase II Trial of First-line Osimertinib for Patients with EGFR Mutation-positive Non-small Cell Lung Cancer and Poor Performance Status (OPEN/TORG2040).

Introduction: Osimertinib is the first-line treatment for patients with non-small cell lung cancer (NSCLC) who have EGFR mutations and favorable performance status (PS). Despite increasing clinical data on osimertinib, evidence in patients with an impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib for patients with EGFR mutation-positive NSCLC and poor PS.

Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer: Results From TROPiCS-03.

Introduction: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).

Methods: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study in solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one prior line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle.

Co-existence of two bla and bla on distinct plasmids in a carbapenem-resistant Klebsiella pneumoniae from a tertiary hospital, Tanzania.

Purpose: To understand the mechanisms of carbapenem-resistant Klebsiella pneumoniae (CRKP) from Tanzania and characterize the genomes carrying the carbapenemase genes.

Methods: Clinical CRKP isolates were selected from ongoing antimicrobial-resistant surveillance at Muhimbili National Hospital, Dar es Salaam, Tanzania. Whole-genome sequencing was performed utilizing Illumina and Nanopore platforms.

Detecting changes of testicular interstitial cell membranes with a fluorescent probe after incubation and cryopreservation with cryoprotective agents.

Membrane alterations are among central factors predetermining cell survival during cryopreservation. In the present research, we tested some serum-/xeno-free cryoprotective compositions including dimethyl sulfoxide (MeSO) and polymers for their osmotic impact and toxicity towards testicular interstitial cells (ICs). IC survival was determined after their contact with MeSO, dextran (D40), hydroxyethyl starch (HES), polyethylene glycols (PEG1500 and PEG400), or after cryopreservation and cryoprotective agent (CPA) removal.

Circular RNAs as Key Regulators in Cancer Hallmarks: New Progress and Therapeutic Opportunities.

Circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, contributing to various cancer hallmarks, including cell proliferation, apoptosis, metastasis, and drug resistance. Defined by their covalently closed loop structure, circRNAs possess unique characteristics like high stability, abundance, and tissue-specific expression. These non-coding RNAs function through mechanisms such as miRNA sponging, interactions with RNA-binding proteins (RBPs), and modulating transcription and splicing.

Host hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury.

Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.

Classes of outpatient quality of care among individuals with substance-related disorders, based on a survey and health insurance registry.

Objectives: Improving quality of care for individuals with substance-related disorders (SRD) should be a priority considering SRD are associated with high morbidity. This study aimed to identify classes of individuals with SRD based on their clinical characteristics and the quality of outpatient care they received, and to verify whether better quality of care was associated with other respondent characteristics and more favorable subsequent outcomes.

Methods: Data came from the 2023-14 and 2015-16 Canadian Community Health Survey (N = 42,099), merged with administrative data from Quebec's health insurance registry.

A Guide to Pathophysiology, Signaling Pathways, and Preclinical Models of Liver Fibrosis.

Liver fibrosis is potentially a reversible form of liver disease that evolved from the early stage of liver scarring as a consequence of chronic liver injuries. Recurrent injuries in the liver without any appropriate medication cause the injuries to get intense and deeper, which gradually leads to the progression of irreversible cirrhosis or carcinoma. Unfortunately, there are no approved treatment strategies for reversing hepatic fibrosis, making it one of the significant risk factors for developing advanced liver disorders and liver disease-associated mortality.

Single versus Dual Antiplatelet Therapy after Left Atrial Appendage Closure: a Propensity Score Matching Analysis.

Background: Either dual antiplatelet therapy or oral anticoagulation in combination with aspirin represent recommended treatment regimens following left atrial appendage closure (LAAC). As the majority of patients receiving LAAC have high bleeding risk, less aggressive antithrombotic treatments are needed, such as single antiplatelet therapy.

Objectives: To compare both ischemic and bleeding outcomes in patients receiving single (SAPT) or dual antiplatelet therapy (DAPT) after successful LAAC.

Investigating the anticancer properties of urolithin B in triple negative breast cancer: In vivo and in vitro insights.

Breast cancer (BC) is a leading cause of cancer-related mortality among women worldwide, with incidence rates rising globally. Urolithin B (UB), a bioactive metabolite of ellagic acid, has demonstrated promising anticancer effects in various cancer models. This study aimed to evaluate the effects of UB on the growth, angiogenesis, and metastasis of BC cells using both in vivo and in vitro approaches.

Prediction of real-time cine-MR images during MRI-guided radiotherapy of liver cancer using a GAN-ConvLSTM network.

Background: Respiratory motion during radiotherapy (RT) may reduce the therapeutic effect and increase the dose received by organs at risk. This can be addressed by real-time tracking, where respiration motion prediction is currently required to compensate for system latency in RT systems. Notably, for the prediction of future images in image-guided adaptive RT systems, the use of deep learning has been considered.

Adoptive T cell therapy targeting an inducible and broadly shared product of aberrant mRNA translation.

Prolonged exposure to interferon-gamma (IFNγ) and the associated increased expression of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) create an intracellular shortage of tryptophan in the cancer cells, which stimulates ribosomal frameshifting and tryptophan to phenylalanine (W>F) codon reassignments during protein synthesis. Here, we investigated whether such neoepitopes can be useful targets of adoptive T cell therapy. Immunopeptidomic analyses uncovered hundreds of W>F neoepitopes mainly presented by the HLA-A24:02 allele.

The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells.

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for targeting "undruggable" proteins, and several PROTACs have reached the stage of clinical candidates. However, the roles of cellular transmembrane transporters in PROTAC uptake and efflux remain underexplored.

Elevating VAPB-PTPIP51 integration repairs damaged mitochondria-associated endoplasmic reticulum membranes and inhibits lung fibroblasts activation.

Long-term silica exposure to silica dust leads to irreversible pulmonary fibrosis, during which lung fibroblast activation plays an essential role. Mitochondria-associated endoplasmic reticulum membranes (MAMs) is a structural interface for communication between the outer mitochondrial membrane and the endoplasmic reticulum. VAPB-PTPIP51 is a key complex on MAMs.

Role of TRIM29 in disease: What is and is not known.

Tripartite motif-containing proteins (TRIMs), comprising the greatest subfamily of E3 ubiquitin ligases with approximately 80 members of this family, are widely distributed in mammalian cells. TRIMs actively participate in ubiquitination of target proteins, a type of post-translational modification associated with protein degradation and other functions. Tripartite motif-containing protein 29 (TRIM29), a member of the TRIM family, differs from other members of this family in that it lacks the RING finger structural domain containing cysteine and histidine residues that mediates DNA binding, protein-protein interactions, and ubiquitin ligase, at its N-terminus.

Shared chemoresistance genes in ESCC and cervical Cancer: Insights from pharmacogenomics and Mendelian randomization.

Background: Neoadjuvant chemotherapy, particularly the use of platinum-based compounds and taxanes, is pivotal in the treatment of epithelial-derived tumors, such as cervical cancer and esophageal squamous cell carcinoma (ESCC); however, resistance remains a significant challenge. Utilizing Mendelian randomization (MR) with pharmacogenomics offers a novel approach to understanding the genetic underpinnings of drug responses, thereby aiding in personalized treatment.

Methods: Single-cell RNA sequencing (scRNA-seq) analysis revealed a shared cellular subpopulation of CD8 + T effector memory (CD8 + TEM) cells that are pivotal in mediating chemotherapy resistance in ESCC and cervical cancer.

Hederagenin ameliorates ferroptosis-induced damage by regulating PPARα/Nrf2/GPX4 signaling pathway in HT22 cells: An in vitro and in silico study.

Background: Hederagenin (HG), derived from ivy seeds, is known to offer protection against Alzheimer's disease (AD). However, the specific molecular pathways through which it counters ferroptosis-induced neurotoxicity are not fully elucidated. This investigation seeks to delineate the processes by which HG mitigates neurotoxic effects in HT22 cells subjected to glutamate (Glu)-induced ferroptosis.

Synthesis and potential anti-inflammatory response of indole and amide derivatives of ursolic acid in LPS-induced RAW 264.7 cells and systemic inflammation mice model: Insights into iNOS, COX2 and NF-κB.

Ursolic acid (3-hydroxy-urs-12-ene-28-oic acid, UA) is a pentacyclic triterpene present in numerous plants, fruits and herbs and exhibits various pharmacological effects. However, UA has limited clinical applicability since it is classified as BCS class IV molecule, characterized by low solubility, low oral bioavailability and low permeability. In the present study, UA was isolated from the biomass marc of Lavandula angustifolia and was structurally modified by an induction of indole ring at the C-3 position and amide group at the C-17 position with the aim to enhance its pharmacological potential.