Side- and Disease-Dependent Changes in Human Aortic Valve Cell Population and Transcriptomic Heterogeneity Determined by Single-Cell RNA Sequencing.

Background: Calcific aortic valve disease (CAVD) is a highly prevalent disease, especially in the elderly population, but there are no effective drug therapies other than aortic valve repair or replacement. CAVD develops preferentially on the fibrosa side, while the ventricularis side remains relatively spared through unknown mechanisms. We hypothesized that the fibrosa is prone to the disease due to side-dependent differences in transcriptomic patterns and cell phenotypes.

AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity.

The forward design of biosensors that implement Boolean logic to improve detection precision primarily relies on programming genetic components to control transcriptional responses. However, cell- and gene-free nanomaterials programmed with logical functions may present lower barriers for clinical translation. Here we report the design of activity-based nanosensors that implement AND-gate logic without genetic parts via bi-labile cyclic peptides.

Novel radiogenomics approach to predict and characterize pneumonitis in stage III NSCLC.

Unresectable stage III NSCLC is now treated with chemoradiation (CRT) followed by immune checkpoint inhibitors (ICI). Pneumonitis, a common CRT complication, has heightened risk with ICI, potentially causing severe outcomes. Currently, there are no biomarkers to predict pneumonitis risk or differentiate between radiation-induced pneumonitis (RTP) and ICI-induced pneumonitis (IIP).

FAK activity exacerbates disturbed flow-mediated atherosclerosis via VEGFR2-Cbl-NF-κB signaling.

Atherosclerosis develops at predictable sites in the vasculature where branch points and curvatures create non-laminar disturbed flow. This disturbed flow causes vascular inflammation by increased endothelial cell (EC) barrier permeability and the expression of inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1). Vascular endothelial growth factor receptor 2 (VEGFR2) is important for flow-induced EC inflammation; however, there are still some gaps in the signaling pathway.

Center of mass states render multijoint torques throughout standing balance recovery.

Successful reactive balance control requires coordinated modulation of hip, knee, and ankle torques. Stabilizing joint torques arise from neurally-mediated feedforward tonic muscle activation that modulates muscle short-range stiffness, which provides instantaneous "mechanical feedback" to the perturbation. In contrast, neural feedback pathways activate muscles in response to sensory input, generating joint torques after a delay.

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.

Differentiating Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases With Emphasis on Pathological and Molecular Considerations: Recommendations From the International Association for the Study of Lung Cancer Pathology Committee.

Introduction: With the implementation of low-dose computed tomography screening, multiple pulmonary tumor nodules are diagnosed with increasing frequency and the selection of surgical treatments versus systemic therapies has become challenging on a daily basis in clinical practice. In the presence of multiple carcinomas, especially adenocarcinomas, pathologically determined to be of pulmonary origin, the distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is important for staging, management, and prognostication.

Methods: We systemically reviewed various means that aid in the differentiation between SPLCs and IPMs explored by histopathologic evaluation and molecular profiling, the latter includes DNA microsatellite analysis, array comparative genomic hybridization, TP53 and oncogenic driver mutation testing and, more recently, with promising effectiveness, next-generation sequencing comprising small- or large-scale multi-gene panels.

Machine learning in image-based outcome prediction after radiotherapy: A review.

The integration of machine learning (ML) with radiotherapy has emerged as a pivotal innovation in outcome prediction, bringing novel insights amid unique challenges. This review comprehensively examines the current scope of ML applications in various treatment contexts, focusing on treatment outcomes such as patient survival, disease recurrence, and treatment-induced toxicity. It emphasizes the ascending trajectory of research efforts and the prominence of survival analysis as a clinical priority.

Antigen-specific T cell immunotherapy by in vivo mRNA delivery.

Immunotherapy has shown promise for treating patients with autoimmune diseases or cancer, yet treatment is associated with adverse effects associated with global activation or suppression of T cell immunity. Here, we developed antigen-presenting nanoparticles (APNs) to selectively engineer disease antigen (Ag)-specific T cells by mRNA delivery. APNs consist of a lipid nanoparticle core functionalized with peptide-major histocompatibility complexes (pMHCs), facilitating antigen-specific T cell transfection through cognate T cell receptor-mediated endocytosis.

Computational staining of CD3/CD20 positive lymphocytes in human tissues with experimental confirmation in a genetically engineered mouse model.

Introduction: Immune dysregulation plays a major role in cancer progression. The quantification of lymphocytic spatial inflammation may enable spatial system biology, improve understanding of therapeutic resistance, and contribute to prognostic imaging biomarkers.

Methods: In this paper, we propose a knowledge-guided deep learning framework to measure the lymphocytic spatial architecture on human H&E tissue, where the fidelity of training labels is maximized through single-cell resolution image registration of H&E to IHC.

Machine Vision-Detected Peritumoral Lymphocytic Aggregates Are Associated With Disease-Free Survival in Patients With Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, with a disease recurrence rate of around 20%. Lymphoid formations, which occur in nonlymphoid tissues during chronic inflammatory, infectious, and immune responses, have been linked with tumor suppression. Lymphoid aggregates potentially enhance the body's antitumor response, offering an avenue for attracting tumor-infiltrating lymphocytes and fostering their coordination.

40 Hz sensory stimulation enhances CA3-CA1 coordination and prospective coding during navigation in a mouse model of Alzheimer's disease.

40 Hz sensory stimulation ("flicker") has emerged as a new technique to potentially mitigate pathology and improve cognition in mouse models of Alzheimer's disease (AD) pathology. However, it remains unknown how 40 Hz flicker affects neural codes essential for memory. Accordingly, we investigate the effects of 40 Hz flicker on neural representations of experience in the hippocampus of the 5XFAD mouse model of AD by recording 1000s of neurons during a goal-directed spatial navigation task.

Organellular imaging reveals a depletion of endoplasmic reticular calcium during post-ictal cortical spreading depolarization.

During cortical spreading depolarization (CSD), neurons exhibit a dramatic increase in cytosolic calcium, which may be integral to CSD-mediated seizure termination. This calcium increase greatly exceeds that during seizures, suggesting the calcium source may not be solely extracellular. Thus, we sought to determine if the endoplasmic reticulum (ER), the largest intracellular calcium store, is involved.

Laterality of Radiation Therapy in Breast Cancer is Not Associated With Increased Risk of Coronary Artery Disease in the Contemporary Era.

Purpose: External beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesized that there is no difference in the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left versus right-sided radiation.

Methods And Materials: For the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022.

Motion and temporal B-shift corrections for QSM and mapping using dual-echo spiral navigators and conjugate-phase reconstruction.

Purpose: To develop an efficient navigator-based motion and temporal B-shift correction technique for 3D multi-echo gradient-echo (ME-GRE) MRI for quantitative susceptibility mapping (QSM) and mapping.

Theory And Methods: A dual-echo 3D stack-of-spiral navigator was designed to interleave with the Cartesian multi-echo gradient-echo acquisitions, allowing the acquisition of both low-echo and high-echo time signals. We additionally designed a novel conjugate phase-based reconstruction method for the joint correction of motion and temporal B shifts.

Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures.

Temporal lobe epilepsy (TLE) is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures.

Gait signature changes with walking speed are similar among able-bodied young adults despite persistent individual-specific differences.

Understanding individuals' distinct movement patterns is crucial for health, rehabilitation, and sports. Recently, we developed a machine learning-based framework to show that "gait signatures" describing the neuromechanical dynamics governing able-bodied and post-stroke gait kinematics remain individual-specific across speeds. However, we only evaluated gait signatures within a limited speed range and number of participants, using only sagittal plane (i.

Effects of acute hippocampal stimulation in the nonhuman primate penicillin model of temporal lobe seizures.

Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts.

Combination of optical coherence tomography-derived shape and texture features are associated with development of sub-foveal geographic atrophy in dry AMD.

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss. Identifying patients with greatest risk of GA progression is important for targeted utilization of emerging therapies. This study aimed to comprehensively evaluate the role of shape-based fractal dimension features ( ) of sub-retinal pigment epithelium (sub-RPE) compartment and texture-based radiomics features ( ) of Ellipsoid Zone (EZ)-RPE and sub-RPE compartments for risk stratification for subfoveal GA (sfGA) progression.