Inhibition of Retinal Neovascularization by BEZ235: Targeting the Akt/4EBP1/Cyclin D1 Pathway in Endothelial Cells.

Purpose: To investigate the therapeutic efficacy of BEZ235, a dual PI3K/mTOR inhibitor, in suppressing pathological neovascularization in an oxygen-induced retinopathy (OIR) mouse model and explore the role of cyclin D1 in endothelial cell cycle regulation.

Methods: Single-cell RNA sequencing was performed to analyze gene expression and cell-cycle alterations in retinal endothelial cells under normoxic and OIR conditions. The effects of BEZ235 on human umbilical vein endothelial cells (HUVECs) and human retinal microvascular endothelial cells (HRMECs) were evaluated by assessing cell viability, cell-cycle progression, proliferation, migration, and tube formation.

The Digital Health Competencies in Medical Education Framework: An International Consensus Statement Based on a Delphi Study.

Importance: Rapid digitalization of health care and a dearth of digital health education for medical students and junior physicians worldwide means there is an imperative for more training in this dynamic and evolving field.

Objective: To develop an evidence-informed, consensus-guided, adaptable digital health competencies framework for the design and development of digital health curricula in medical institutions globally.

Evidence Review: A core group was assembled to oversee the development of the Digital Health Competencies in Medical Education (DECODE) framework.

Survival Among Patients With ERBB2-Positive Metastatic Breast Cancer and Central Nervous System Disease.

Importance: Approximately one-third of patients with ERBB2 (formerly HER2 or HER2/neu)-positive (ERBB2+) metastatic breast cancer (MBC) develop brain metastasis. It is unclear whether patients with disease limited to the central nervous system (CNS) have different outcomes and causes of death compared with those with concomitant extracranial metastasis.

Objective: To assess overall survival (OS) and CNS-related mortality among patients with ERBB2+ breast cancer and a diagnosis of CNS disease by disease distribution (CNS only vs CNS plus extracranial metastasis).

Minimally invasive biomarkers for triaging lung nodules-challenges and future perspectives.

CT chest scans are commonly performed worldwide, either in routine clinical practice for a wide range of indications or as part of lung cancer screening programs. Many of these scans detect lung nodules, which are small, rounded opacities measuring 8-30 mm. While the concern about nodules is that they may represent early lung cancer, in screening programs, only 1% of such nodules turn out to be cancer.

From fatty liver to fibrosis: the impact of miRNAs on NAFLD and NASH.

Non-alcoholic fatty liver disease (NAFLD) is a disease with various levels varying from fatty liver steatosis to acute steatosis which is non-alcoholic steatohepatitis (NASH), which can develop into hepatic failure, as well as in some conditions it can develop into hepatocellular carcinoma (HCC). In the NAFLD and NASH context, aberrant microRNA (miRNA) expression has a thorough contribution to the incidence and development of these liver disorders by influencing key biological actions, involving lipid metabolism, inflammation, and fibrosis. Dysregulated miRNAs can disrupt the balance between lipid accumulation and clearance, exacerbate inflammatory responses, and promote fibrogenesis, thus advancing the severeness of the disorder from simple steatosis to more complex NASH.

Upregulation of the MAP2K4 gene triggers endothelial-mesenchymal transition in COVID-19.

Background: SARS-CoV-2 infection is marked by an excessive inflammatory response, leading to elevated production of pro-inflammatory cytokines through activation of intracellular pathways like mitogen-activated protein kinase (MAPK). Viruses can use the MAPK signaling pathway to their advantage, but the relationship of this pathway to the severe SARS-CoV-2 period has not been fully elucidated. MAP2K4 is involved in the MAPK signaling pathway and affects cellular processes such as cell-cell junction, cell proliferation, differentiation and apoptosis.

Innovative approaches to large lower calyceal stones (10-20 mm): evaluating modified T-tilt position and lower calyx hydrodilatation techniques in flexible ureteroscopy versus hydrodilatation alone: prospective randomized controlled study.

Background: Managing lower calyceal stones poses significant challenges. Flexible ureteroscopy and laser lithotripsy (FURSL) are standard techniques for treating large stones (10-20 mm).

Objective: This study evaluates the role of the T-tilt position (45-degree Trendelenburg with a 45-degree lateral tilt against the side of the stone) and hydrodilatation of the lower calyx with 50 cc saline injection as needed in optimizing stone-free rates and safety during FURSL for lower calyceal stones.

Comparison of surgical approaches and outcome for symptomatic pineal cysts: microscopic/endoscopic fenestration vs. stereotactic catheter implantation.

Purpose: Treatment strategies for space-occupying/symptomatic pineal cysts (PC) are still up for debate. In this study we present PC management, outcome data and risk factors for recurrence after surgery, focusing on microscopic/endoscopic procedures vs. stereotactic catheter implantation as alternative treatment concept to permanently drain PC into ventricles/cisterns.

Ebastine-mediated destabilization of E3 ligase MKRN1 protects against metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition encompassing metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), which can progress to fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). The heterogeneous and complex nature of MASLD complicates optimal drug development. Ebastine, an antihistamine, exhibits antitumor activity in various types of cancer.

Individual management and prognostic assessment for long-term outcomes using a novel classification system of craniopharyngiomas: a retrospective study of single institution.

Purpose: This study aims to propose a classification system to more accurately understand the features and nature of different CPs, to investigate the correlation between different topographies of CPs and their surgical outcomes.

Methods: A retrospective analysis was conducted on 91 surgically resected CPs. They were categorized into six types based on their location and origin.

Maxillary canting and anatomical variation relevant to Le Fort I osteotomy: a morphometric study using cone beam computed tomography.

Purpose: To investigate the anatomical variations and measure the distances between surgically relevant structures in the maxilla associated with Le Fort I osteotomy in patients with maxillary canting using cone beam computed tomography (CBCT).

Methods: CBCT scans of 63 patients (21 males and 42 females) with maxillary canting who were indicated for orthognathic surgical planning were retrospectively investigated and analyzed. The distances of the relevant anatomical structures, including the descending palatine artery, pterygomaxillary junction, infraorbital foramen, and nasolacrimal duct opening, were measured with the key anatomical landmarks to evaluate their variations.

Biomarker microRNA-371a-3p - expression in malignancies other than germ-cell tumours.

Purpose: microRNA-371a-3p (M371) is considered a highly sensitive and specific serum biomarker of testicular germ cell tumours (GCTs). However, little is known about the expression of M371 in nontesticular malignancies (NTMs), so far. As knowledge about the expression of the marker in other malignancies is a prerequisite for the clinical application of the test we aimed to explore the M371 expression in other cancers.

Long-term effects of superselective renal artery embolization on renal function after percutaneous nephrolithotomy.

Objectives: To investigate the long-term impact of superselective renal artery embolization (SRAE) on renal function in cases of severe post-percutaneous nephrolithotomy (PCNL) haemorrhage, and to identify the factors associated with the long-term outcome of renal function.

Methods: Patients treated with SRAE for post-PCNL hemorrhage between September 2016 and September 2021 were included. Patients' demographic and clinical data were recorded.

Understanding the anatomical basis of anorectal fistulas and their surgical management: exploring different types for enhanced precision and safety.

Anorectal fistulas remain one of the most challenging conditions in colorectal surgery and require precise anatomical knowledge for successful management. This comprehensive review synthesizes the current evidence on the anatomical foundations of fistula development and treatment, particularly focusing on the cryptoglandular hypothesis and its clinical implications. A systematic analysis of the recent literature has examined the relationship between anatomical structures and fistula formation, classification systems, diagnostic modalities, and therapeutic approaches.

From smog to scarred hearts: unmasking the detrimental impact of air pollution on myocardial ischemia-reperfusion injury.

Air pollution is a global environmental health hazard associated with elevated cardiovascular morbidity and mortality. Emerging evidence suggests that exposure to various air pollutants, specifically particulate matter (PM), ultrafine particulate matter (UFPM), and diesel exhaust particles, may exacerbate myocardial ischemia-reperfusion (I/R) injury. PM exposure can directly impair cardiomyocyte survival under ischemic conditions by inducing inflammation, oxidative stress, apoptosis, and dysregulation of non-coding RNAs.

Investigation of the antibacterial activity, cytotoxicity, and effects on enamel and composite resin of mouthwash formulations prepared with three different Boron compounds.

Objective: This study investigated the use of oral rinse solutions formulated with boron-containing compounds, known for their antibacterial activity, as an alternative to chlorhexidine (CHX).

Material And Method: Boron nitride (BN), boric acid (BA) and sodium borate (SB) were used in the study. BN was used in nanosuspension (BN-NS) due to its low solubility in water.

Application of novel strategies in chronic wound management with focusing on pressure ulcers: new perspective.

Invading blood cells, extracellular tissue, and soluble mediators all play important roles in the wound-healing process. There is a substantial global burden of disease and mortality attributable to skin defects that do not heal. About 1% to 2% of the population in industrialized nations suffers from chronic wounds that don't heal, despite healthcare breakthroughs; this condition is very costly, costing about $25 billion each year in the US alone.

Acute and chronic cannabis vapor exposure produces immediate and delayed impacts on phases of fear learning in a sex specific manner.

Rationale: Current treatment options for PTSD have unreliable efficacy, with many individuals unable to achieve complete remission. Cannabis and cannabinoids that act through the endogenous cannabinoid (endocannabinoid) system to help promote trauma recovery by means of enhanced extinction learning are potential therapeutic, pharmacological candidates. Using a preclinical model of translationally-relevant cannabis administration in rodents, we examined the impact of cannabis exposure on aversive memory.

ICTV Virus Taxonomy Profile: 2025.

is a family of plant viruses with tripartite, positive-sense RNA genomes of about 8 kb in total. Genomic RNAs are packaged in separate virions that may also contain sub-genomic, defective or satellite RNAs. Virions are variable in morphology (spherical or bacilliform) and may be transmitted between hosts mechanically, via pollen, or non-persistently by insect vectors.

Periductal fibroblasts participate in liver homeostasis, fibrosis, and tumorigenesis.

Hepatic fibroblasts comprise groups of stromal cells in the liver that are phenotypically distinct from hepatic stellate cells. However, their physiology is poorly understood. By single-cell RNA sequencing, we identified Cd34 and Dpt as hepatic fibroblast-specific genes.

Gestational arsenite exposure alters maternal postpartum heart size and induces Ca-handling dysregulation in cardiomyocytes.

Cardiovascular disease is the leading cause of mortality in the US. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health.

Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy.

Mutations occurring in the MeCp2, CDKL5 and BDNF genes have been linked to epileptogenesis in various epilepsy syndromes. This study employed bioinformatics analysis of transcriptomic data to examine the interrelationship among these genes in both epileptic and healthy individuals. Moreover, we assessed the expression of MeCp2, CDKL5 and BDNF at both mRNA and protein levels in human hippocampal tissues obtained from 22 patients undergoing epilepsy surgery for mesial temporal lobe epilepsy (MTLE) as well as from 25 autopsied specimens.

Lipid Profile, PCSK9, ANGPTL3 and Lipoprotein (a) Levels in Men Diagnosed With Localized High-Grade Prostate Cancer and Men At-Risk of Prostate Cancer.

Background: Some cancers have been found to require abundant supplies of lipids for their development. One example is prostate cancer (PCa). To date, lipid-modifying factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like 3 protein (ANGPTL3), and lipoprotein(a) or Lp(a), have not been reported in men with PCa.

Histone methyltransferase KMT2A promotes pulmonary fibrogenesis via targeting pro-fibrotic factor PU.1 in fibroblasts.

Background: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease driven by both environmental and genetic factors. Epigenetics refers to changes in gene expression or cellular phenotype that do not involve alterations to DNA sequence. KMT2A is a member of the SET family which catalyses H3K4 methylation.

Metastatic Thymic Mucoepidermoid Carcinoma: The Diagnostic Challenges and Role of CRTC1/MAML2 Translocation in Accurate Diagnosis and Treatment.

Mucoepidermoid carcinoma (MEC) is a subtype of epithelial neoplasms commonly found in salivary glands, but can also be seen in the thymus. Diagnosing MEC of the thymus is sometimes challenging due to its histological similarities with adenosquamous carcinoma (ASC). This case report describes a 64-year-old female with a history of metastatic endometrial adenocarcinoma who presented to an oncology clinic with a thymic mass as well as multiple mass lesions in the liver, bone, and abdominal wall.