Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Dissecting contributions of pulmonary arterial remodeling to right ventricular afterload in pulmonary hypertension.

Pulmonary hypertension (PH) is defined as an elevation in the right ventricle (RV) afterload, characterized by increased hemodynamic pressure in the main pulmonary artery (PA). Elevations in RV afterload increase RV wall stress, resulting in RV remodeling and potentially RV failure. From a biomechanical standpoint, the primary drivers for RV afterload elevations include increases in pulmonary vascular resistance (PVR) in the distal vasculature and decreases in vessel compliance in the proximal PA.

In-silico CT lung phantom generated from finite-element mesh.

Several lung diseases lead to alterations in regional lung mechanics, including ventilator- and radiation-induced lung injuries. Such alterations can lead to localized underventilation of the affected areas, resulting in the overdistension of the surrounding healthy regions. Thus, there has been growing interest in quantifying the dynamics of the lung parenchyma using regional biomechanical markers.

Patient-specific 3D modeling and fluid dynamic analysis of primary pulmonary vein stenosis.

Introduction: Primary pulmonary vein stenosis (PVS) is a rare congenital heart disease that proves to be a clinical challenge due to the rapidly progressive disease course and high rates of treatment complications. PVS intervention is frequently faced with in-stent restenosis and persistent disease progression despite initial venous recanalization with balloon angioplasty or stenting. Alterations in wall shear stress (WSS) have been previously associated with neointimal hyperplasia and venous stenosis underlying PVS progression.

Physics-informed motion registration of lung parenchyma across static CT images.

Lung injuries, such as ventilator-induced lung injury and radiation-induced lung injury, can lead to heterogeneous alterations in the biomechanical behavior of the lungs. While imaging methods, e.g.

Right ventricular stiffening and anisotropy alterations in pulmonary hypertension: Mechanisms and relations to function.

Aims: Pulmonary hypertension (PH) results in an increase in RV afterload, leading to RV dysfunction and failure. The mechanisms underlying maladaptive RV remodeling are poorly understood. In this study, we investigated the multiscale and mechanistic nature of RV free wall (RVFW) biomechanical remodeling and its correlations with RV function adaptations.

Targeted Rapamycin Delivery via Magnetic Nanoparticles to Address Stenosis in a 3D Bioprinted in Vitro Model of Pulmonary Veins.

Vascular cell overgrowth and lumen size reduction in pulmonary vein stenosis (PVS) can result in elevated PV pressure, pulmonary hypertension, cardiac failure, and death. Administration of chemotherapies such as rapamycin have shown promise by inhibiting the vascular cell proliferation; yet clinical success is limited due to complications such as restenosis and off-target effects. The lack of in vitro models to recapitulate the complex pathophysiology of PVS has hindered the identification of disease mechanisms and therapies.

Review of Gold Nanoparticles in Surface Plasmon-Coupled Emission Technology: Effect of Shape, Hollow Nanostructures, Nano-Assembly, Metal-Dielectric and Heterometallic Nanohybrids.

Point-of-care (POC) diagnostic platforms are globally employed in modern smart technologies to detect events or changes in the analyte concentration and provide qualitative and quantitative information in biosensing. Surface plasmon-coupled emission (SPCE) technology has emerged as an effective POC diagnostic tool for developing robust biosensing frameworks. The simplicity, robustness and relevance of the technology has attracted researchers in physical, chemical and biological milieu on account of its unique attributes such as high specificity, sensitivity, low background noise, highly polarized, sharply directional, excellent spectral resolution capabilities.

An image-driven micromechanical approach to characterize multiscale remodeling in infarcted myocardium.

Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework to elucidate the fiber-level remodeling mechanisms that drive tissue-level adaptation for each subject.

Discovery of benzoxazole-thiazolidinone hybrids as promising antibacterial agents against and species.

Antibiotic resistance is rapidly exacerbating the unceasing rise in nosocomial infections caused by drug-resistant bacterial pathogens such as methicillin-resistant (MRSA), carbapenem-resistant (CRE) and vancomycin-resistant (VRE). Therefore, there is a dire need for new therapeutic agents that can mitigate the unbridled emergence of drug-resistant pathogens. In the present study, several benzoxazole-thiazolidinone hybrids (BT hybrids) were synthesized and evaluated for their antibacterial activity against the ESKAP pathogen panel.

Improved right ventricular strain estimation in rats using anisotropic diffusion filtering.

Calculating cardiac strains through speckle tracking echocardiography (STE) has shown promise as prognostic markers linked to functional indices and disease outcomes. However, the presence of acoustic shadowing often challenges the accuracy of STE in small animals such as rodents. The shadowing arises due to the complex anatomy of rodents, with operator dexterity playing a significant role in image quality.

Volumetric versus distortional deformation in rat lungs.

There are several lung diseases that lead to alterations in regional lung mechanics, including acute respiratory distress syndrome. Such alterations can lead to localized underventilation of the affected areas resulting in the overdistension of the surrounding healthy regions. They can also lead to the surrounding alveoli expanding unevenly or distorting.

A Micro-anatomical Model of the Infarcted Left Ventricle Border Zone to Study the Influence of Collagen Undulation.

Myocardial infarction (MI) results in cardiac myocyte death and often initiates the formation of a fibrotic scar in the myocardium surrounded by a border zone. Myocyte loss and collagen-rich scar tissue heavily influence the biomechanical behavior of the myocardium which could lead to various cardiac diseases such as systolic heart failure and arrhythmias. Knowledge of how myocyte and collagen micro-architecture changes affect the passive mechanical behavior of the border zone remains limited.

Smartphone-Based Attomolar Cyanide Ion Sensing Using Au-Graphene Oxide Cryosoret Nanoassembly and Benzoxazolium-Based Fluorophore in a Surface Plasmon-Coupled Enhanced Fluorescence Interface.

Photoplasmonic platforms are being demonstrated as excellent means for bridging nanochemistry and biosensing approaches at advanced interfaces, thereby augmenting the sensitivity and quantification of the desired analytes. Although resonantly coupled electromagnetic waves at the surface plasmon-coupled emission (SPCE) interface are investigated with myriad nanomaterials in order to boost the detection limits, rhodamine moieties are ubiquitously used as SPCE reporter molecules in spite of their well-known limitations. In order to overcome this constraint, in this work, a benzoxazolium-based fluorescent molecule, ()-2-(4-(dimethylamino)styryl)-3-methylbenzo[]oxazol-3-ium iodide (), was synthesized to selectively detect the cyanide (CN) ions in water samples.

Multiscale characterization of left ventricle active behavior in the mouse.

The myocardium possesses an intricately designed microarchitecture to produce an optimal cardiac contraction. The contractile behavior of the heart is generated at the sarcomere level and travels across several length scales to manifest as the systolic function at the organ level. While passive myocardial behavior has been studied extensively, the translation of active tension produced at the fiber level to the organ-level function is not well understood.

Disease progression modeling of the North Star Ambulatory Assessment for Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by decreased or absent dystrophin gene leading to progressive muscle degeneration and weakness in young boys. Disease progression models for the North Star Ambulatory Assessment (NSAA), a functional measurement widely used to assess outcomes in clinical trials, were developed using a longitudinal population modeling approach. The relationship between NSAA total score over time, loss of ambulation, and potential covariates that may influence disease progression were evaluated.

Spinal Morphometry As A Novel Predictor For Recurrent Lumbar Disc Herniation Requiring Revision Surgery: Results of A Case Control Study.

Introduction: There is conflicting data on the risk factors for recurrent lumbar disc herniation (rLDH). Most of the predictors for rLDH identified so far are acquired risk factors or radiological factors at the level of the herniation. Whole lumbar spine (WLS) morphometry has not been evaluated as a possible predictor of rLDH.

Contractile Adaptation of the Left Ventricle Post-myocardial Infarction: Predictions by Rodent-Specific Computational Modeling.

Myocardial infarction (MI) results in cardiac myocyte death and the formation of a fibrotic scar in the left ventricular free wall (LVFW). Following an acute MI, LVFW remodeling takes place consisting of several alterations in the structure and properties of cellular and extracellular components with a heterogeneous pattern across the LVFW. The normal function of the heart is strongly influenced by the passive and active biomechanical behavior of the LVFW, and progressive myocardial structural remodeling can have a detrimental effect on both diastolic and systolic functions of the LV leading to heart failure.

Graphitic Carbon Cloth-Based Hybrid Molecular Catalyst: A Non-conventional, Synthetic Strategy of the Drop Casting Method for a Stable and Bifunctional Electrocatalyst for Enhanced Hydrogen and Oxygen Evolution Reactions.

Hydrogen energy production through water electrolysis is envisaged as one of the most promising, sustainable, and viable alternate sources to cater to the incessant demands of renewable energy storage. Germane to our effort in this field, we report easily synthesizable and very cost-effective isoperthiocyanic acid (IPA) molecular complexes as electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) under acidic and alkaline conditions. The Pd(II)IPA, Co(II)IPA, and Ni(II)IPA complexes were synthesized and were evaluated for HER and OER applications.

Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications.

Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients.

Design, synthesis and screening of benzoxazole-thiazolidinone hybrids as potential inhibitors of SARS-CoV-2 proteases.

Hybrid molecules in the recent years have gained significant importance in drug research as promising therapeutic agents. We report a novel combination of two such bioactive scaffolds (benzoxazole and 4-thiazolidinone B-T hybrids) as inhibitors of SARS-CoV-2. The study uses an approach to identify the potential of B-T hybrids as possible inhibitors of the SARS-CoV-2 proteases.

Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of the protein dystrophin. Gene therapy strategies that aim to increase expression of a functional dystrophin protein (mini-dystrophin) are under investigation. The ability to accurately quantify dystrophin/mini-dystrophin is essential in assessing the level of gene transduction.

Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis.

Background: The first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted the safety and efficacy of PF-06480605 in ulcerative colitis. Preclinical and in vitro models have identified a role for TL1A in both innate and adaptive immune responses, but the mechanisms underlying the efficacy of anti-TL1A treatment in inflammatory bowel disease (IBD) are not known.