Virtual screening: hope, hype, and the fine line in between.

Introduction: Technological advancements in virtual screening (VS) have rapidly accelerated its application in drug discovery, as reflected by the exponential growth in VS-related publications. However, a significant gap remains between the volume of computational predictions and their experimental validation. This discrepancy has led to a rise in the number of unverified 'claimed' hits which impedes the drug discovery efforts.

Total autologous reconstruction of the right and left ventricular outflow tracts: the case for the modified Ross-Ozaki procedure.

The Ross procedure continues to be the best procedure to address unrepairable aortic valve pathology, especially in young adults. The Achilles heel of this procedure has been aortic root dilation and the potential need for a reoperation that may be associated with slightly increased risks in addition to the need for intervention on the pulmonary outflow tract. Modifying the Ross procedure by autograft inclusion inside a Dacron graft seems to have the potential advantage of stabilizing the autograft diameter, which may be associated with improved durability and decrease the need for future intervention.

Intrapericardial Corticosteroids and Colchicine Prevent Pericarditis and Atrial Fibrillation After Epicardial Ablation of Ventricular Arrhythmias.

Background: Postprocedural pericarditis (PP) can occur in up to 29.4% of patients undergoing epicardial catheter ablation of ventricular tachycardia (VT). Despite several proposed strategies to mitigate this adverse outcome, rates of PP and pericarditic pain remain high.

Endoscopic management of bleeding ectopic varices: multicentric retrospective case series.

Introduction: Portal hypertension is a common complication of liver cirrhosis. Varices are dilated collaterals that develop as a result of portal hypertension at the level of the porto-systemic connections and can cause a shift in the blood flow from high to low pressure. Common locations for porto-systemic shunts are the lower oesophagus and the gastric fundus.

Response of to zinc and silicon nanoparticles and pollen extract as alternates to traditional fertilizers.

is used in a variety of medicinal and aromatic products. The effects of various treatments on sage () plants were investigated in an open-field experiment conducted between 2021 and 2022. During the experiment, ZnO nanoparticles (NPs) were used at concentrations of 1.

Management of Complex Postburn Scar Contracture of the Dorsum of Pediatric Hand.

This case report details the challenging management of a 3-year-old girl with a severe left-hand extension contracture resulting from a scald burn. Delayed presentation prompted a 2-stage surgical approach. The first stage involved excising contracted skin and using a groin flap for reconstruction.

From Virtual Screens to Cellular Target Engagement: New Small Molecule Ligands for the Immune Checkpoint LAG-3.

Herein, we performed a virtual screening study to discover new scaffolds for small molecule-based ligands of the immune checkpoint lymphocyte-activation gene 3 (LAG-3). Molecular dynamics (MD) simulations using the LAG-3 structure revealed two putative binding sites for small molecules: the antibody interface and the lipophilic canyon. A 3D pharmacophore screening resulted in the identification of potential ligands for these binding sites and afforded a library of 25 compounds.

Burkholderia cepacia Infective Endocarditis of Native Aortic Valve: A Case Report and Review of Literature.

Infective endocarditis (IE) is a serious cardiac infection of the endocardium, native and prosthetic valves, or cardiac device. In this case study, we report a case of an immunocompetent patient with severe aortic valve endocarditis. A 54-year-old female presented to the emergency department with progressive shortness of breath, chest pain, palpitations, and cough for a period of 20 days.

Small molecules from antibody pharmacophores (SMAbPs) as a hit identification workflow for immune checkpoints.

Small-molecule modulators of immune checkpoints are poised to revolutionize cancer immunotherapy. However, efficient strategies for hit identification are lacking. We introduce small molecules from antibody pharmacophores (SMAbPs), a workflow leveraging cocrystal structures of checkpoints with antibodies to create pharmacophore maps for virtual screening.

Design and Biophysical Characterization of Second-Generation cyclic peptide LAG-3 inhibitors for cancer immunotherapy.

Lymphocyte activation gene 3 (LAG-3) is an inhibitory immune checkpoint crucial for suppressing the immune response against cancer. Blocking LAG-3 interactions enables T cells to recover their cytotoxic capabilities and diminishes the immunosuppressive effects of regulatory T cells. A cyclic peptide (Cys-Val-Pro-Met-Thr-Tyr-Arg-Ala-Cys, disulfide bridge: 1-9) was recently reported as a LAG-3 inhibitor.

Evaluating the reproductive performance of Summan grouper, (Forsskal, 1775), in the Red Sea.

Grouper fish are among the most important components of the fisheries of many countries because they are found in warm water throughout the world. There are 15 genera and 159 species known worldwide; 8 genera and 66 species are exclusively found in the western Indian Ocean, Red Sea, and Arabian Gulf. The Summan grouper, , constitutes a considerable portion of these fisheries; therefore, this study aimed to evaluate the reproductive strategy of this important fish species.

Discovery of ICOS-Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening.

Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS-L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules.

Discovery of ICOS-targeted small molecules using affinity selection mass spectrometry screening.

Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS-L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules.

Modulation of naïve mesenchymal stromal cells by extracellular vesicles derived from insulin-producing cells: an in vitro study.

This study was to determine whether extracellular vesicles (EVs) derived from insulin-producing cells (IPCs) can modulate naïve mesenchymal stromal cells (MSCs) to become insulin-secreting. MSCs were isolated from human adipose tissue. The cells were then differentiated to generate IPCs by achemical-based induction protocol.

Measures to Prevent Infection in Cardiac Implantable Electronic Device Replacements or Upgrades.

Cardiac implantable electronic device (CIED) infections represent one of the most threatening complications associated with device implantation, due to an increase in morbidity and mortality rates, as well as healthcare costs. Besides, it is important to highlight that when compared to the initial implantation of a device, the risks associated with procedures like generator changes, lead and pocket revisions, or device upgrades double. Consequently, to address this issue, various scoring systems, like the PADIT (Prior Procedures, Age, Depressed Renal Function, Immunocompromised Status, Type of Procedure), the RI-AIAC (Ricerca Sulle Infezioni Associate a ImpiAnto o Sostituzione di CIED), and the Shariff score, along with predictive models, have been developed to identify patients at a greater risk of infection.

High-frequency low-tidal volume ventilation improves procedural and long-term clinical outcomes in persistent atrial fibrillation ablation: Prospective multicenter registry.

Background: High-frequency, low-tidal volume (HFLTV) ventilation increases the efficacy and efficiency of radiofrequency catheter ablation (RFCA) of paroxysmal atrial fibrillation. Whether those benefits can be extrapolated to RFCA of persistent atrial fibrillation (PeAF) is undetermined.

Objective: The purpose of this study was to evaluate whether using HFLTV ventilation during RFCA in patients with PeAF is associated with improved procedural and long-term clinical outcomes compared to standard ventilation (SV).

Structure-Based Rational Design of Constrained Peptides as TIM-3 Inhibitors.

Blocking the immunosuppressive function of T-cell immunoglobulin mucin-3 (TIM-3) is an established therapeutic strategy to maximize the efficacy of immune checkpoint inhibitors for cancer immunotherapy. Currently, effective inhibition of TIM-3 interactions relies on monoclonal antibodies (mAbs), which come with drawbacks such as immunogenicity risk, limited tumor penetration, and high manufacturing costs. Guided by the X-ray cocrystal structures of TIM-3 with mAbs, we report an structure-based rational design of constrained peptides as potent TIM-3 inhibitors.

Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells.

Background: Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type 2 diabetes and its complications through their immunomodulatory and differentiation capabilities. However, the hyperglycaemia of the diabetic microenvironment may exert a detrimental effect on the functionality of ASCs.

Feasibility, Efficacy, and Safety of Fluoroless Ablation of VT in Patients With Structural Heart Disease.

Background: Catheter ablation of ventricular tachycardia (VT) typically requires radiation exposure with its potential adverse health effects. A completely fluoroless ablation approach is achievable using a combination of electroanatomical mapping and intracardiac echocardiography. Nonetheless, data in patients undergoing VT ablation are limited.