Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models.

The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses ( wild-type, -mutated, -mutated, and -mutated).

PAC1 Agonist Maxadilan Reduces Atherosclerotic Lesions in Hypercholesterolemic ApoE-Deficient Mice.

A possible involvement of immune- and vasoregulatory PACAP signaling at the PAC1 receptor in atherogenesis and plaque-associated vascular inflammation has been suggested. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE atherosclerosis model for possible effects on atherogenesis. Adult male ApoE mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treated with Maxadilan, M65 or Sham.

Predictive Value of Inflammatory Scores for Left Atrium Thrombosis in Ischemic Stroke Without Atrial Fibrillation.

: Studies have shown that inflammation markers can be used as prognostic tools in predicting acute ischemic stroke. In this study, we conducted a comparison of several inflammation scores in predicting left atrial thrombosis (LAT) in patients with ischemic stroke without AF. : In this single-center, retrospective study, we included 303 consecutive patients with ischemic stroke.

Results of Modified Minimally Invasive Hallux Valgus Surgery, Factors for the First Metatarsal Shortening, and Patients' Satisfaction.

: Hallux valgus is a prevalent foot deformity conventionally treated with open surgical techniques, which carry risk of complications due to extensive soft tissue dissection. Minimally invasive surgeries (MISs) as alternatives offer comparable outcomes, reduced pain, and faster recovery; however, their challenges include the risk of shortening of the first metatarsal. This study aimed to assess the efficacy of our modified MIS hallux valgus correction technique and investigate the factors that affect first metatarsal shortening.

The Influence of Long COVID on the Cardiovascular System and Predictors of Long COVID in Females: Data from the Polish Long COVID Cardiovascular (PoLoCOV-CVD) Study.

Female sex is one of the Long COVID (LC) risk factors; however, the LC predictors in females have not been established. This study was conducted to assess the influence of LC on the cardiovascular system and to assess the age-independent predictors of LC in females. : Patient information and the course of the disease with symptoms were collected in women at least 12 weeks after COVID-19 recovery.

Two Different Hemodynamic Responses in ME/CFS Patients with Postural Orthostatic Tachycardia Syndrome During Head-Up Tilt Testing.

: While the diagnosis of postural orthostatic tachycardia syndrome (POTS) is based on heart rate (HR) and blood pressure (BP) criteria, the pathophysiology of POTS is not fully understood as multiple pathophysiological mechanisms have been recognized. Also, cardiac function, being dependent on preload, afterload, contractility, and HR, has not been properly studied. Preload and contractility changes can be inferred from stroke volume index (SVI) changes during a tilt test.

Comparative Analysis of Outcomes in Adult Spinal Deformity Patients with Proximal Junctional Kyphosis or Failure Initially Fused to Upper Versus Lower Thoracic Spine.

Patients with proximal junctional kyphosis (PJK) or failure (PJF) may demonstrate disparate outcomes and recovery when fused to the upper (UT) versus lower (LT) thoracic spine. Few studies have distinguished the reoperation and recovery abilities of patients with PJK or PJF when fused to the upper (UT) versus lower (LT) thoracic spine. Adult spine deformity patients ≥ 18 yrs with preoperative and 5-year (5Y) data fused to the sacrum/pelvis were included.

The Impact of Comorbid Sleep-Disordered Breathing on Hospitalization Risk Related to Diabetes and Atherosclerotic Disease: A Retrospective Cohort Analysis.

To determine the relationship between comorbid sleep-disordered breathing (SDB) and hospitalization rates related to diabetes mellitus (DM) and atherosclerotic disease (AD). This study used a retrospective cohort design from a large medical claims database with 5 years of data between 2018 and 2022. The presences of SDB, DM, and AD were identified using International Classification of Diseases (ICD-10) and relevant Current Procedural Terminology (CPT) codes.

Catheter Ablation in Atrial Fibrillation: Recent Advances.

Atrial fibrillation (AF) is the leading cause of arrhythmia-related morbidity and mortality. Recurrent symptoms, hospitalizations, and cost burden to patients have necessitated treatments beyond antiarrhythmic drugs (AADs) for patients with AF. Catheter ablation has proven to be effective over medical therapy alone; however the recurrence rates for atrial tachyarrhythmias post-ablation remain significant, particularly in patients with persistent and long-standing persistent AF.

Nanomedicine in Ophthalmology: From Bench to Bedside.

Ocular diseases such as cataract, refractive error, age-related macular degeneration, glaucoma, and diabetic retinopathy significantly impact vision and quality of life worldwide. Despite advances in conventional treatments, challenges like limited bioavailability, poor patient compliance, and invasive administration methods hinder their effectiveness. Nanomedicine offers a promising solution by enhancing drug delivery to targeted ocular tissues, enabling sustained release, and improving therapeutic outcomes.

Double-J Ureteral Stenting in Obstetrics and Gynecology: Pivotal or Problematic?

: Double-J stents are urinary catheters that are frequently used in urology. They are now also used in other specialist areas such as obstetrics and gynecology. However, the use of double-J stents is not without side effects.

Pulmonary Embolism Response Teams-Evidence of Benefits? A Systematic Review and Meta-Analysis.

Venous thromboembolisms constitute a major cause of morbidity and mortality with 60,000 to 100,000 deaths attributed to pulmonary embolism in the US annually. Both clinical presentations and treatment strategies can vary greatly, and the selection of an appropriate therapeutic strategy is often provider specific. A pulmonary embolism response team (PERT) offers a multidisciplinary approach to clinical decision making and the management of high-risk pulmonary emboli.

Efficacy of Dietary Interventions for Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Irritable bowel syndrome (IBS) is a common condition that alters the quality of life of patients. A variety of dietary interventions have been introduced to address this debilitating condition. The low-FODMAP diet (LFD), gluten-free diet (GFD), and Mediterranean diet are examples showing efficacy.

Validation Against Polysomnography of a Transthoracic Impedance Sensor for Screening of Sleep Apnea in Heart Failure Patients: A Pooled Analysis of AIRLESS and UPGRADE.

Cardiac implantable electronic devices and their integrated thoracic impedance sensors have been used to detect sleep apnea for over a decade now. Despite their usage in daily clinical practice, there are only limited data on their diagnostic accuracy. AIRLESS and UPGRADE were prospective investigator-driven trials meant to validate the AP scan (Boston Scientific, Marlborough, MA, USA) in heart failure cohorts.

Identification of Potential Sepsis Therapeutic Drugs Using a Zebrafish Rapid Screening Approach.

In the military, combat wound infections can progress rapidly to life-threatening sepsis. The discovery of effective small-molecule drugs to prevent and/or treat sepsis is a priority. To identify potential sepsis drug candidates, we used an optimized larval zebrafish model of endotoxicity/sepsis to screen commercial libraries of drugs approved by the U.

Effects of High-Intensity Interval Training on Blood Pressure Levels in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Objective: This systematic review and meta-analysis aimed to (I) evaluate the evidence on the effects of high-intensity interval training (HIIT) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients; (II) determine whether HIIT impacts SBP and DBP differently; and (III) assess the clinical relevance of these effects.

Methods: A comprehensive search was conducted across multiple electronic databases, resulting in the inclusion of seven randomized clinical trials in the meta-analysis. The outcomes were analyzed using random-effects models to compute mean differences (MD) and standardized mean differences (SMD) for SBP and DBP.

Mechanisms of Cbl-Mediated Ubiquitination of Proteins in T and Natural Killer Cells and Effects on Immune Cell Functions.

Post-translational ubiquitination is an essential mechanism for the regulation of protein stability and function, which contributes to the regulation of the immune system. Cbl, an E3 ubiquitin ligase, is particularly well-characterized in the context of T and NK cell signaling, where it serves as a key regulator of receptor downstream signaling events and as a modulator of cell activation. Cbl promotes the proteasomal degradation of TCR/CD3 subunits as well as the protein kinases Fyn and Lck in T cells.

Advances in Topical Therapies for Clinically Relevant and Prevalent Forms of Alopecia.

Alopecia encompasses diverse conditions that vary by etiology, progression, and clinical presentation, including androgenetic alopecia, alopecia areata, telogen effluvium, and scarring alopecias such as lichen planopilaris and central centrifugal cicatricial alopecia. Managing these conditions requires tailored therapeutic approaches, with topical treatments emerging as effective first-line interventions. This literature review examines topical therapies across alopecia types, assessing mechanisms of action, clinical efficacy, and safety profiles to guide evidence-based clinical practice.

GPR68 Mediates Lung Endothelial Dysfunction Caused by Bacterial Inflammation and Tissue Acidification.

Tissue acidification resulting from dysregulated cellular bioenergetics accompanies various inflammatory states. GPR68, along with other members of proton-sensing G protein-coupled receptors, responds to extracellular acidification and has been implicated in chronic inflammation-related diseases such as ischemia, cancer, and colitis. The present study examined the role of extracellular acidification on human pulmonary endothelial cell (EC) permeability and inflammatory status per se and investigated potential synergistic effects of acidosis on endothelial dysfunction caused by bacterial lipopolysaccharide (LPS, ).

Modeling Viral Capsid Assembly: A Review of Computational Strategies and Applications.

Viral capsid assembly is a complex and critical process, essential for understanding viral behavior, evolution, and the development of antiviral treatments, vaccines, and nanotechnology. Significant progress in studying viral capsid assembly has been achieved through various computational approaches, including molecular dynamics (MD) simulations, stochastic dynamics simulations, coarse-grained (CG) models, electrostatic analyses, lattice models, hybrid techniques, machine learning methods, and kinetic models. Each of these techniques offers unique advantages, and by integrating these diverse computational strategies, researchers can more accurately model the dynamic behaviors and structural features of viral capsids, deepening our understanding of the assembly process.

Co-Inhibition of tGLI1 and GP130 Using FDA-Approved Ketoconazole and Bazedoxifene Is Synergistic Against the Growth and Metastasis of HER2-Enriched and Triple-Negative Breast Cancers.

Breast cancer stem cells (CSCs) are resistant to most cancer therapeutics and contribute to tumor recurrence and metastasis. Two breast CSC-promoting transcription factors, truncated glioma-associated oncogene homolog 1 (tGLI1) and signal transducer and activator of transcription 3 (STAT3), have been reported to be frequently co-expressed in HER2-enriched breast cancer and triple-negative breast cancer (TNBC), undergo protein-protein interactions for gene regulation and activation, and functionally cooperate to promote breast CSCs. STAT3 can be activated by activated interleukin-6 receptor/glycoprotein-130 (IL-6R/GP130).

Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis.

Metarrestin (ML246) is a first-in-class pyrrole-pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in solid tumor cells. The occurrence of PNC demonstrates a positive correlation with malignancy, serving as an indicator of tumor aggressiveness, progression, and metastasis.

Enhancing the Opportunistic Bone Status Assessment Using Radiomics Based on Dual-Energy Spectral CT Material Decomposition Images.

Unlabelled: The dual-energy spectral CT (DEsCT) employs material decomposition (MD) technology, opening up novel avenues for the opportunistic assessment of bone status. Radiomics, a powerful tool for elucidating the structural and textural characteristics of bone, aids in the detection of mineral loss. Therefore, this study aims to compare the efficacy of bone status assessment using both bone density measurements and radiomics models derived from MD images and to further explore the clinical value of radiomics models.

Game-Based Digital Interventions for Enhancing Positive Development and Addressing Substance Use in Adolescents: A Systematic Review.

This study systematically reviewed research on the use of digital game approaches for the prevention, assessment, and treatment of substance use and positive development in adolescents. : This study aimed to identify and summarize gaps in the published literature on game-based digital interventions for substance use and positive development for adolescents through a systematic review. : Following PRISMA guidelines, 26 studies were selected for final analysis from an initial screening of 1601 references.

Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.

Infantile spasms are common in Down Syndrome (DS), but the mechanisms by which DS predisposes to this devastating epilepsy syndrome are unclear. In general, neuronal excitability and therefore seizure predisposition results from an imbalance of excitation over inhibition in neurons and neural networks of the brain. Animal models provide clues to mechanisms and thereby provide potential therapeutic approaches.