EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate.

MYC is one of the most important therapeutic targets in human cancer. Many attempts have been made to develop small molecules that could be used to curb its activity in patients, but most failed to identify a suitable direct inhibitor. After years of preclinical characterization, a tissue-penetrating peptide MYC inhibitor, called Omomyc, has been recently successfully used in a Phase I dose escalation study in late-stage, all-comers solid tumour patients.

The effects of real vs simulated high altitude on associative memory for emotional stimuli.

Introduction: This study aimed to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on associative memory performance for emotionally valenced stimuli.

Methods: Two experiments were conducted. In Study 1, n = 18 undergraduates performed an associative memory task under three NH conditions (FiO= 20.

Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity.

Nitric oxide (NO) has been defined as the "miracle molecule" due to its essential pleiotropic role in living systems. Besides its implications in physiologic functions, it is also involved in the development of several disease states, and understanding this ambivalence is crucial for medicinal chemists to develop therapeutic strategies that regulate NO production without compromising its beneficial functions in cell physiology. Although nitric oxide synthase (NOS), i.

Three-Dimensional Analysis of the Maxillary Sinuses in Ancient Crania Dated to the V-VI Centuries BCE from Opi (Italy): Volumetric Measurements in Ancient Skulls from the Necropolis of Opi, Abruzzi, Italy.

Cone beam computed tomography (CBCT) can provide precise information about complex anatomical structures as it is characterised by rapid volumetric image acquisition with high resolution. The aim of this study was to provide measurements for 20 ancient skulls of the Samnite people found in the necropolis of Opi, a small and isolated mountain village in Abruzzo, a region in central Italy. All the images (left and right) of the 20 ancient skulls from Opi were acquired.

Combining the Fragment Molecular Orbital and GRID Approaches for the Prediction of Ligand-Metalloenzyme Binding Affinity: The Case Study of hCA II Inhibitors.

Polarization and charge-transfer interactions play an important role in ligand-receptor complexes containing metals, and only quantum mechanics methods can adequately describe their contribution to the binding energy. In this work, we selected a set of benzenesulfonamide ligands of human Carbonic Anhydrase II (hCA II)-an important druggable target containing a Zn ion in the active site-as a case study to predict the binding free energy in metalloprotein-ligand complexes and designed specialized computational methods that combine the ab initio fragment molecular orbital (FMO) method and GRID approach. To reproduce the experimental binding free energy in these systems, we adopted a machine-learning approach, here named formula generator (FG), considering different FMO energy terms, the hydrophobic interaction energy (computed by GRID) and logP.

Mechanobiological Strategies to Enhance Ovine () Adipose-Derived Stem Cells Tendon Plasticity for Regenerative Medicine and Tissue Engineering Applications.

Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold.

DNA Damage Response in Early Breast Cancer: A Phase III Cohort in the Phobos Study.

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model.

Good Initial Visual Acuity in Patients with Macular Edema due to Retinal Vein Occlusion - Management and Outcomes.

Purpose: The approach to managing patients with retinal vein occlusion (RVO) and cystoid macular edema (CME) with good initial visual acuity (VA) better than 6/12 has not been investigated. This study aimed to evaluate functional and anatomical outcomes of intravitreal treatment and observation in patients with CME due to RVO, who presented with good initial VA. Methods: Multicenter retrospective cohort study.

Combining Intravenous Thrombolysis and Dual Antiplatelet Treatment in Patients With Minor Ischemic Stroke: A Propensity Matched Analysis of the READAPT Study Cohort.

Background: The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS.

Biomechanical factors and atherosclerosis localization: insights and clinical applications.

Although the entire vascular bed is constantly exposed to the same risk factors, atherosclerosis manifests a distinct intra-individual pattern in localization and progression within the arterial vascular bed. Despite shared risk factors, the development of atherosclerotic plaques is influenced by physical principles, anatomic variations, metabolic functions, and genetic pathways. Biomechanical factors, particularly wall shear stress (WSS), play a crucial role in atherosclerosis and both low and high WSS are associated with plaque progression and heightened vulnerability.

From self-Assembly to healing: Engineering ultra-Small peptides into supramolecular hydrogels for controlled drug release.

The aim of this study was the evaluation of suitability of novel mucoadhesive hydrogel platforms for the delivery of therapeutics useful for the management of disorders related to the gastrointestinal tract (GI). At this purpose, here we describe the preparation, the physicochemical characterization and drug delivery behaviour of novel hydrogels, based on self-assembling lipopeptides (MPD02-09), obtained by covalently conjugating lauric acid (LA) to SNA's peptide derivatives gotten by variously combining D- and L- amino acid residues. LA conjugation was aimed at improving the stability of the precursor peptides, obtaining amphiphilic structures, and triggering the hydrogels formation through the self-assembling.

Clinical characteristics and treatment approach of established New-Onset status epilepticus (eNOSE): A Real-World multicenter experience.

Introduction: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context.

Exploring the accuracy of tooth loss prediction between a clinical periodontal prognostic system and a machine learning prognostic model.

Aim: The aim of this analysis was to compare a clinical periodontal prognostic system and a developed and externally validated artificial intelligence (AI)-based model for the prediction of tooth loss in periodontitis patients under supportive periodontal care (SPC) for 10 years.

Materials And Methods: Clinical and radiographic parameters were analysed to assign tooth prognosis with a tooth prognostic system (TPS) by two calibrated examiners from different clinical centres (London and Pittsburgh). The prediction model was developed on the London dataset.

Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence.

Acinetobacter baumannii is a critical opportunistic pathogen associated with nosocomial infections. The high rates of antibiotic-resistance acquisition make most antibiotics ineffective. Thus, new medical countermeasures are urgently needed.

Ex Vivo Lenticule Customization for Stromal Lenticule Addition Keratoplasty.

Purpose: The purpose of this study was to explore the optimal shape of customized lenticules for stromal lenticule addition keratoplasty (SLAK) for off-centered ectasia.

Methods: Two different methods to create ex vivo models of eccentric-keratoconus were investigated. Twelve human corneas were used to create model 1 by a hyperopic photorefractive keratectomy (PRK), and model 2 by masked phototherapeutic keratectomy (PTK) on the anterior corneal surface, whereas both types received myopic ablation of the posterior surface.

Design, Synthesis, and Anti-Prostate Cancer Potential of 2-(4-Nitrobenzyl) Malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo.

New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods.

Workload of home care nurses: Italian adaptation, validity, and reliability of the National Aeronautics and Space Administration Task Load Index questionnaire.

The aim of this study was to adapt the National Aeronautics and Space Administration Task Load Index (NASA-TLX) to the home care setting and translate and validate it in Italian. An online questionnaire containing the Italian version of the NASA-TLX adapted to the home care setting was administered to home care nurses to measure workload. Content Validity Index, Exploratory, and Confirmatory Factor Analyses were used to measure the psychometric characteristics of the modified NASA-TLX.

Context matters: task relevance shapes neural responses to emotional facial expressions.

Recent research shows that emotional facial expressions impact behavioral responses only when their valence is relevant to the task. Under such conditions, threatening faces delay attentional disengagement, resulting in slower reaction times and increased omission errors compared to happy faces. To investigate the neural underpinnings of this phenomenon, we used functional magnetic resonance imaging to record the brain activity of 23 healthy participants while they completed two versions of the go/no-go task.

High-flow nasal cannula and in-line aerosolised bronchodilator delivery during severe exacerbation of asthma in adults: a feasibility observational study.

Background: Asthma is a common chronic respiratory disease affecting 1-29% of the population in different countries. Exacerbations represent a change in symptoms and lung function from the patient's usual condition that requires emergency department (ED) admission. Recently, the use of a High-Flow Nasal Cannula (HFNC) plus an in-line vibrating mesh nebulizer (VMN) for aerosol drug delivery has been advocated in clinical practice.

Staphylococcus aureus/Staphylococcus epidermidis from skin microbiota are balanced by Pomegranate peel extract: An eco-sustainable approach.

The imbalance in skin microbiota is characterized by an increased number of pathogens in respect to commensal microorganisms. Starting from a skin microbiota collection, the aim of this work was to evaluate the possible role of Pomegranate (Punica granatum L.) Peel Extract (PPE) in restoring the skin microbiota balance acting on Staphylococcus spp.