Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies.

Colorectal cancer patients-derived immunity-organoid platform unveils cancer-specific tissue markers associated with immunotherapy resistance.

Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness.

A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer's Disease.

Background: CT1812 is a first-in-class, sigma-2 receptor ligand, that prevents and displaces binding of amyloid beta (Aβ) oligomers. Normalization of quantitative electroencephalography (qEEG) markers suggests that CT1812 protects synapses from Aβ oligomer toxicity.

Objectives: Evaluate CT1812 impact on synaptic function using qEEG measurements.

CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.

Introduction: CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.

Methods: Unbiased analysis of tandem-mass tag mass spectrometry (TMT-MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282).

An interim exploratory proteomics biomarker analysis of a phase 2 clinical trial to assess the impact of CT1812 in Alzheimer's disease.

CT1812 is a novel, brain penetrant small molecule modulator of the sigma-2 receptor (S2R) that is currently in clinical development for the treatment of Alzheimer's disease (AD). Preclinical and early clinical data show that, through S2R, CT1812 selectively prevents and displaces binding of amyloid beta (Aβ) oligomers from neuronal synapses and improves cognitive function in animal models of AD. SHINE is an ongoing phase 2 randomized, double-blind, placebo-controlled clinical trial (COG0201) in participants with mild to moderate AD, designed to assess the safety and efficacy of 6 months of CT1812 treatment.

Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer's disease.

Synapse loss correlates with cognitive decline in Alzheimer's disease, and soluble oligomeric amyloid beta (Aβ) is implicated in synaptic dysfunction and loss. An important knowledge gap is the lack of understanding of how Aβ leads to synapse degeneration. In particular, there has been difficulty in determining whether there is a synaptic receptor that binds Aβ and mediates toxicity.

A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer's disease.

Background: Effective, disease-modifying therapeutics for the treatment of Alzheimer's disease (AD) remain a large unmet need. Extensive evidence suggests that amyloid beta (Aβ) is central to AD pathophysiology, and Aβ oligomers are among the most toxic forms of Aβ. CT1812 is a novel brain penetrant sigma-2 receptor ligand that interferes with the binding of Aβ oligomers to neurons.

Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy.

Sigma-2 Receptors-From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases.

There is a large unmet medical need to develop disease-modifying treatment options for individuals with age-related degenerative diseases of the central nervous system. The sigma-2 receptor (S2R), encoded by , is expressed in brain and retinal cells, and regulates cell functions via its co-receptor progesterone receptor membrane component 1 (PGRMC1), and through other protein-protein interactions. Studies describing functions of S2R involve the manipulation of expression or pharmacological modulation using exogenous small-molecule ligands.

Suppressed-scattering spectral windows for radiative cooling applications.

The scattering of light by resonant nanoparticles is a key process for enhancing the solar reflectance in daylight radiative cooling. Here, we investigate the impact of material dispersion on the scattering performance of popular nanoparticles for radiative cooling applications. We show that, due to material dispersion, nanoparticles with a qualitatively similar response at visible frequencies exhibit fundamentally different scattering properties at infrared frequencies.

Energy in Construction and Building Materials.

Energy efficiency in buildings has become a major challenge in both science and industry [...

Higher general executive functions predicts lower body mass index by mitigating avoidance behaviors.

Background: The present study examines the relationship between obesity, executive functions, and body image in a nonclinical population from southern Italy.

Methods: General executive functioning (Frontal Assessment Battery-15), and body image disturbances (Body Uneasiness Test) were assessed in a sample including 255 participants (138 females, M age = 43.51 years, SD = 17.

A double-blind, placebo-controlled, single-ascending-dose intravenous infusion study of rHIgM22 in subjects with multiple sclerosis immediately following a relapse.

Background: Recombinant human immunoglobulin M22 (rHIgM22) has promoted remyelination in animal models and was well tolerated in people with clinically stable multiple sclerosis.

Objective: Safety/tolerability of a single rHIgM22 dose was investigated following an acute relapse and to determine whether this enhanced CNS/CSF concentrations.

Methods: Adults (N = 27) with acute relapse were assigned to rHIgM22 (0.

Low-Cycle Fatigue of FRP Strips Glued to a Quasi-Brittle Material.

This paper aims at further advancing the knowledge about the cyclic behavior of FRP strips glued to quasi-brittle materials, such as concrete. The results presented herein derive from a numerical model based on concepts of based on fracture mechanics and already presented and validated by the authors in previous works. Particularly, it assumes that fracture processes leading to debonding develop in pure mode II, as is widely accepted in the literature.

A Review on Cementitious Self-Healing and the Potential of Phase-Field Methods for Modeling Crack-Closing and Fracture Recovery.

Improving the durability and sustainability of concrete structures has been driving the enormous number of research papers on self-healing mechanisms that have been published in the past decades. The vast developments of computer science significantly contributed to this and enhanced the various possibilities numerical simulations can offer to predict the entire service life, with emphasis on crack development and cementitious self-healing. The aim of this paper is to review the currently available literature on numerical methods for cementitious self-healing and fracture development using Phase-Field (PF) methods.

Analytical Modeling of the Postcracking Response Observed in Hybrid Steel/Polypropylene Fiber-Reinforced Concrete.

This study deals with the analytical modeling of hybrid fiber-reinforced concretes (HyFRCs) made with a blend of different types of fibers characterized by different geometries and/or constitutive materials. The presented analytical formulation is oriented towards predicting the postcracking behavior of HyFRC and is mainly based on the well-known "cracked-hinge" model originally employed for standard fiber-reinforced concrete beams. The proposed model is validated by considering the experimental results obtained in a previous study carried out on HyFRCs mixtures made with a blend of steel and polypropylene fibers.

Optimization of Multilayered Walls for Building Envelopes Including PCM-Based Composites.

This work proposes a numerical procedure to simulate and optimize the thermal response of a multilayered wallboard system for building envelopes, where each layer can be possibly made of Phase Change Materials (PCM)-based composites to take advantage of their Thermal-Energy Storage (TES) capacity. The simulation step consists in solving the transient heat conduction equation across the whole wallboard using the enthalpy-based finite element method. The weather is described in detail by the Typical Meteorological Year (TMY) of the building location.

A Comparative Study on the Thermal Energy Storage Performance of Bio-Based and Paraffin-Based PCMs Using DSC Procedures.

Thermal-Energy Storage (TES) properties of organic phase change materials have been experimentally investigated and reported in this paper. Three paraffin-based Phase Change Materials (PCMs) and one bio-based PCM are considered with melting temperatures of 24 °C, 25 °C and 26 °C. Sensible heat storage capacities, melting characteristics and latent heat enthalpies of the studied PCMs are investigated through Differential Scanning Calorimetry (DSC) measurements.

The clinical promise of biomarkers of synapse damage or loss in Alzheimer's disease.

Background: Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.

Modelling the Thermal Energy Storage of Cementitious Mortars Made with PCM-Recycled Brick Aggregates.

This paper reports a numerical approach for modelling the thermal behavior and heat accumulation/liberation of sustainable cementitious composites made with Recycled Brick Aggregates (RBAs) employed as carriers for Phase-Change Materials (PCMs). In the framework of the further development of the fixed grid modelling method, classically employed for solving the well-known Stefan problem, an enthalpy-based approach and an apparent calorific capacity method have been proposed and validated. More specifically, the results of an experimental program, following an advanced incorporation and immobilization technique, developed at the for investigating the thermal responses of various combinations of PCM-RBAs, have been considered as the benchmark to calibrate/validate the numerical results.

Chondroitinase improves anatomical and functional outcomes after primate spinal cord injury.

Inhibitory extracellular matrices form around mature neurons as perineuronal nets containing chondroitin sulfate proteoglycans that limit axonal sprouting after CNS injury. The enzyme chondroitinase (Chase) degrades inhibitory chondroitin sulfate proteoglycans and improves axonal sprouting and functional recovery after spinal cord injury in rodents. We evaluated the effects of Chase in rhesus monkeys that had undergone C7 spinal cord hemisection.

Characterization of a New Dry Drill-Milling Process of Carbon Fibre Reinforced Polymer Laminates.

Carbon Fibre Reinforced Polymer (CFRP) composites are widely used in aerospace applications that require severe quality parameters. To simplify the assembly operations and reduce the associated costs, the current trend in industry is to optimize the drilling processes. However, the machining of CFRP composites is very challenging compared with metals, and several defect types can be generated by drilling.