Unveiling the Potential of C Factor Applied to Pilot Bioavailability/Bioequivalence Studies-A Case Study with Pazopanib Drug Products.

When companies are uncertain about the potential of a new formulation to be bioequivalent to a Reference product, it is common practice to carry out downsized pilot studies as a gatekeeping in vivo strategy to decide whether to move forward or not with a full-size pivotal study. However, due to the small study size, these studies are inarguably more sensitive to variability. To address and mitigate the uncertainty of the conclusions of pilot studies concerning the maximum observed concentration (C), the factor was proposed as an alternative approach to the average bioequivalence statistical methodology.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Scapulothoracic Disorders: Anatomy, Kinematics, Clinical Assessment, and Multimodality Imaging.

Shoulder and neck concerns are prevalent musculoskeletal issues prompting medical attention, often stemming from scapulothoracic disorders that can serve as both the cause and consequence of other shoulder abnormalities. Scapular dyskinesis, fractures, benign and malignant masses, and neuropathies are frequently overlooked yet can substantially affect shoulder pain and function, particularly in athletes. Scapulothoracic disorders may lead to and/or be worsened by common shoulder abnormalities including those of the rotator cuff, neighboring bursae, and the glenohumeral articulation and labrum.

There is poor agreement between the subjective and quantitative adjudication of aneurysm wall enhancement.

Background And Purpose: The determination of Aneurysm wall enhancement (AWE) by human readers on visual inspection alone is subjective and prone to error. A three-dimensional (3D) method for quantifying the aneurysm wall's signal intensity (SI) enables objective determination of AWE. Inter-reader agreement and agreement between subjective and objective determination of AWE were assessed in this study.

Experimental toothpastes containing β-TCP nanoparticles functionalized with fluoride and tin to prevent Erosive Tooth Wear.

Objectives: The present study aimed to synthesize toothpastes containing Beta- TriCalcium Phosphate (β-TCP) nanoparticles, functionalized with fluoride and tin, and test their ability to reduce erosive tooth wear (ETW).

Methods: Toothpastes were synthesized with the following active ingredients: 1100 ppm of fluoride (as sodium fluoride, F), 3500 ppm of tin (as stannous chloride, Sn), and 800 ppm of β-TCP (Sizes a - 20 nm; and b - 100 nm). Enamel specimens were randomly assigned into the following groups (n = 10): 1.

Young-Onset Alzheimer Dementia Due to a Novel Pathogenic Variant Initially Misdiagnosed as Autoimmune Encephalitis.

Objectives: Pathogenic variants in presenilin 1 are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked.

Impact of COVID-19 Pandemic on Tuberculosis and Latent Tuberculosis Infection Diagnosis in Healthcare Workers.

Objective: The aim of the study is to compare the prevalence of latent tuberculosis infection and tuberculosis (TB) in the prepandemic period (2017-2019) with the pandemic period (2020-2022), in a group of healthcare workers (HCWs).

Methods: This is a retrospective study. Data on TB diagnosis was retrieved from the hospital information system database.

Advanced spectroscopic investigation of colour centres in LiF crystals irradiated with monochromatic hard x-rays.

Nominally-pure lithium fluoride (LiF) crystals were irradiated with monochromatic hard x-rays of energy 5, 7, 9 and 12 keV at the METROLOGIE beamline of the SOLEIL synchrotron facility, in order to understand the role of the selected x-ray energy on their visible photoluminescence (PL) response, which is used for high spatial resolution 2D x-ray imaging detectors characterized by a wide dynamic range. At the energies of 7 and 12 keV the irradiations were performed at five different doses corresponding to five uniformly irradiated areas, while at 5 and 9 keV only two irradiations at two different doses were carried out. The doses were planned in a range between 4 and 1.

Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions.

Patients with sickle cell disease (SCD) display priapism, a prolonged penile erection in the absence of sexual arousal. The current pharmacological treatments for SCD-associated priapism are limited and focused on acute interventions rather than prevention. Thus, there is an urgent need for new drug targets and preventive pharmacological therapies for this condition.

Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models.

A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration.

Associations of Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology in Early Adolescence: A Prospective Population-Based Study.

Background: Arterial wall thickness and stiffness, and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health-related brain changes may be observable already in adolescence.

Exploring the potential of Eu and Mn activated LaAlO phosphors as red and far-red emitters for horticulture lighting.

The development of efficient red and far-red emitters, for efficient plant absorption in the Photosynthetically Active Radiation (PAR) region, holds significance in contemporary plant growth control. This study focuses on the synthesis and characterization of LaAlO as a host material, doped with Eu and Mn ions, using a solid-state reaction method. The investigation encompasses the creation and analysis of both single-doped and co-doped samples, employing techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence (PL) spectroscopy.

Liver Fibrosis, Fat, and Iron Evaluation with MRI and Fibrosis and Fat Evaluation with US: A Practical Guide for Radiologists.

Quantitative imaging biomarkers of liver disease measured by using MRI and US are emerging as important clinical tools in the management of patients with chronic liver disease (CLD). Because of their high accuracy and noninvasive nature, in many cases, these techniques have replaced liver biopsy for the diagnosis, quantitative staging, and treatment monitoring of patients with CLD. The most commonly evaluated imaging biomarkers are surrogates for liver fibrosis, fat, and iron.

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein.

Both T cells and B cells have been shown to be generated after infection with SARS-CoV-2 yet protocols or experimental models to study one or the other are less common. Here, we generate a chimeric protein (SpiN) that comprises the receptor binding domain (RBD) from Spike (S) and the nucleocapsid (N) antigens from SARS-CoV-2. Memory CD4 and CD8 T cells specific for SpiN could be detected in the blood of both individuals vaccinated with Coronavac SARS-CoV-2 vaccine and COVID-19 convalescent donors.

The importance of routine quality control for reproducible pulmonary measurements by in vivo micro-CT.

Micro-computed tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies. The generation of reliable and reproducible experimental data is strictly dependent on a system's stability. Quality controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking.

Evaluating metallic artefact of biodegradable magnesium-based implants in magnetic resonance imaging.

Magnesium (Mg) implants have shown to cause image artefacts or distortions in magnetic resonance imaging (MRI). Yet, there is a lack of information on how the degradation of Mg-based implants influences the image quality of MRI examinations. In this study, Mg-based implants are analysed and in the clinical setting for various magnetic field strengths with the aim to quantify metallic artefact behaviour.

Mass Training In Situ During COVID-19 Pandemic: Enhancing Efficiency and Minimizing Sick Leaves.

Introduction: Avoiding coronavirus disease 2019 (COVID-19) work-related infection in frontline healthcare workers is a major challenge. A massive training program was launched in our university hospital for anesthesia/intensive care unit and operating room staff, aiming at upskilling 2249 healthcare workers for COVID-19 patients' management. We hypothesized that such a massive training was feasible in a 2-week time frame and efficient in avoiding sick leaves.

Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo.

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study.

Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of -Seropositive Individuals.

Background: There are few contemporary cohorts of -seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with seropositivity.

Methods: Participants were selected in blood banks at 2 Brazilian centers.

Osteoblast-Specific Wnt Secretion Is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice.

Wnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in the bone anabolic response to mechanical loading is not well established. Recent transcriptome profiling studies by our laboratory and others show that mechanical loading potently induces genes encoding Wnt ligands, including Wnt1 and Wnt7b. Based on these findings, we hypothesized that mechanical loading stimulates adult bone formation by inducing Wnt ligand expression.

Cardiac microcalcification burden: Global assessment in high cardiovascular risk subjects with Na[F]F PET-CT.

Background: Fluorine-18 sodium fluoride (Na[F]F) atherosclerotic plaque uptake in positron emission tomography with computed tomography (PET-CT) identifies active microcalcification. We aim to evaluate global cardiac microcalcification activity with Na[F]F, as a measure of unstable microcalcification burden, in high cardiovascular (CV) risk patients.

Methods And Results: Thirty-four high CV risk individuals without previous CV events were scanned with Na[F]F PET-CT.