Inhibition of EphA2 by syndecan-4 in wounded skin regulates clustering of fibroblasts.

Upon injury, fibroblasts in the surrounding tissue become activated, migrating into the wound in a controlled manner. Once they arrive, they contract the wound and remodel the stroma. While certain cell surface receptors promote fibroblast migration, others cause repulsion between fibroblasts upon contact, seemingly opposing their clustering within the wound bed.

Intestinal Cyp24a1 regulates vitamin D locally independent of systemic regulation by renal Cyp24a1 in mice.

Vitamin D regulates mineral homeostasis. The most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is synthesized by CYP27B1 from 25-dihydroxyvitamin D (25D) and inactivated by CYP24A1. Human monogenic diseases and genome-wide association studies support a critical role for CYP24A1 in regulation of mineral homeostasis, but little is known about its tissue-specific effects.

Gait Velocity Alterations in Essential Tremor: a Meta-Analysis.

Essential tremor (ET) is a prevalent movement disorder that impairs gait function, including gait speed - a critical marker of mobility disability and adverse outcomes. This meta-analysis aimed to quantify differences in gait speed between individuals diagnosed with ET compared to people without a movement disorder diagnosis. Electronic databases were searched for studies comparing gait speed in ET patients and controls.

Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer.

The interest in galectin-3 as a drug target in the cancer and fibrosis space has grown during the past few years with several new classes of compounds being developed. The first orally available galectin-3 inhibitor, (h-galectin-3 K = 0.025 μM), is currently in phase 2 clinical trials.

Galectin-1 Induces the Production of Immune-Suppressive Cytokines in Human and Mouse T Cells.

Galectin-1 is implicated in several pro-tumourigenic mechanisms and is considered immune-suppressive. The pharmacological inhibition of galectin-1 may be beneficial in cancers in which galectin-1 is overexpressed and driving cancer progression. This study aimed to further characterise the immunosuppressive cytokines influenced by galectin-1 in in vitro immune cell cultures and an in vivo inflammatory model using a recently discovered selective inhibitor of galectin-1, GB1908.

Dosimetric comparison between laterality-specific and general knowledge-based planning models for nonsmall cell lung cancer.

To investigate the dosimetric impact of laterality-specific RapidPlan models for nonsmall cell lung cancer. Three RapidPlan models were developed and validated for Right, Left, and General conventional lung radiotherapy. Each model was trained using 50 plans.

Cross-shaped windows transformer with self-supervised pretraining for clinically significant prostate cancer detection in bi-parametric MRI.

Background: Bi-parametric magnetic resonance imaging (bpMRI) has demonstrated promising results in prostate cancer (PCa) detection. Vision transformers have achieved competitive performance compared to convolutional neural network (CNN) in deep learning, but they need abundant annotated data for training. Self-supervised learning can effectively leverage unlabeled data to extract useful semantic representations without annotation and its associated costs.

Photon-Counting CT in Cancer Radiotherapy: Technological Advances and Clinical Benefits.

Photon-counting computed tomography (PCCT) marks a significant advancement over conventional energy-integrating detector (EID) CT systems. This review highlights PCCT's superior spatial and contrast resolution, reduced radiation dose, and multi-energy imaging capabilities, which address key challenges in radiotherapy, such as accurate tumor delineation, precise dose calculation, and treatment response monitoring. PCCT's improved anatomical clarity enhances tumor targeting while minimizing damage to surrounding healthy tissues.

Vagal stimulation ameliorates murine colitis by regulating SUMOylation.

Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality in mouse models of disease. Conversely, vagal stimulation restored neuromodulation and ameliorated colitis by inhibiting the posttranslational modification SUMOylation through a mechanism independent of the canonical interleukin-10/α7 nicotinic cholinergic vagal pathway.

Osteoarthritis and Neurological Disorder Diagnoses in Adults: A Meta-Analysis Examining Associations With Parkinson's Disease, Multiple Sclerosis, and Alzheimer's Disease.

Osteoarthritis (OA) is a highly prevalent joint disorder that is emerging as a global threat to health. OA is associated with low-grade chronic systemic inflammation that can affect overall health, leading to a sedentary lifestyle and potentially increased risk of neurological disorders (ND) such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). A meta-analysis was conducted following the Preferred Reporting Items for 2020 Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Effect of GB1107, a novel galectin-3 inhibitor on pro-fibrotic signalling in the liver.

Background And Purpose: Galectin-3 (Gal-3) is a pro-fibrotic β-galactoside binding lectin highly expressed in fibrotic liver and implicated in hepatic fibrosis. GB1107 is a novel orally active Gal-3 small molecule inhibitor that has high affinity for Gal-3 >1000-fold selectively over other galectins. The aim of this study was to characterise GB1107 and galectin-3 in vitro and in vivo in the context of fibrosis signalling and liver disease.

Exploring age-related differences in the relationship between spatial and temporal contributions to step length asymmetry during split-belt adaptation.

Gait adaptability is crucial for meeting environmental demands, and impaired gait adaptation increases fall risk, particularly in older adults. While prior research exists on older adults' gait adaptation, particularly in perturbation studies, the specific contributions of temporal and spatial adaptation strategies to step length asymmetry (SLA) during split-belt treadmill walking require further examination. This study fills this gap by evaluating how distinct adaptation strategies contribute to SLA in healthy young and older adults.

The dual timescales of gait adaptation: initial stability adjustments followed by subsequent energetic cost adjustments.

Gait adaptation during bipedal walking allows people to adjust their walking patterns to maintain balance, avoid obstacles and avoid injury. Adaptation involves complex processes that function to maintain stability and reduce energy expenditure. However, the processes that influence walking patterns during different points in the adaptation period remain to be investigated.

Core Modifications of GSK3335103 toward Orally Bioavailable αβ Inhibitors with Improved Synthetic Tractability.

The αβ integrin has been identified as a target for the treatment of fibrotic diseases, based on the role it has in activating TGF-β, a protein implicated in the pathogenesis of fibrosis. However, the development of orally bioavailable αβ inhibitors has proven challenging due to the zwitterionic pharmacophore required to bind to the RGD binding site. This work describes the design and development of a novel, orally bioavailable series of αβ inhibitors, developing on two previously published αβ inhibitors, GSK3008348 and GSK3335103.

Virtual Assessment of Functional Mobility in Lower Extremity Prosthesis Clients: An Exploratory Study.

Objective: To investigate the relationship between patient perception of lower extremity function and a home-based virtual clinician assessment of mobility in lower limb prosthesis clients.

Design: Descriptive observational study using a clinician-administered functional mobility survey and timed Up and Go test to assess lower extremity function under supervision.

Setting: Health Insurance Portability and Accountability Act-compliant online virtual platform.

Ensuring High Quality Treatment Plans with a Plan Quality Review Checklist.

Treatment plan quality is a crucial component for a successful outcome of radiation therapy treatments. As the complexity of radiation therapy planning and delivery techniques increases, the role of the medical physicist in assessing treatment plan quality becomes more critical. Integrating plan quality review throughout the treatment planning process allows improvements without delaying treatment or rushing to produce changes at the last minute.

Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth.

Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if estrogens affect eosinophil biology in tumors and how this influences ICB efficacy has not been determined.

Lung SBRT: Dose gradient optimization based on target size.

This study investigated optimization settings that steepen the dose gradient as a function of target size for lung stereotactic body radiation therapy (SBRT). Sixty-eight lung SBRT patients with planning target volumes (PTVs) ranging from 2-203 cc were categorized into small (<20 cc), medium (20-50 cc), and large (>50 cc) groups. VMAT plans were generated using the normal tissue objective (NTO) to penalize the dose gradient at progressively steeper NTO fall-off values (0.

A lung SBRT treatment planning technique to focus high dose on gross disease.

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the Eclipse treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.

Running Economy Changes Alter Predicted Running Speed and Performance in Collegiate Runners.

The goal of the study was to determine the effect of altering running strategy on predicted running performance in distance runners through application of a novel prediction model. Fifteen male ( = 10; Age: 22.2 ± 4.