Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

Background: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling.

A human breast atlas integrating single-cell proteomics and transcriptomics.

The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation.

Cardiac radiotherapy induces electrical conduction reprogramming in the absence of transmural fibrosis.

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction.

Evaluation of Motion Compensation Methods for Noninvasive Cardiac Radioablation of Ventricular Tachycardia.

Purpose: Noninvasive cardiac radioablation is increasingly used for treatment of refractory ventricular tachycardia. Attempts to limit normal tissue exposure are important, including managing motion of the target. An interplay between cardiac and respiratory motion exists for cardiac radioablation, which has not been studied in depth.

Mechanical Modulation of Ovarian Cancer Tumor Nodules Under Flow.

Objective: Perfusion models are valuable tools to mimic complex features of the tumor microenvironment and to study cell behavior. In ovarian cancer, mimicking disease pathology of ascites has been achieved by seeding tumor nodules on a basement membrane and subjecting them to long-term continuous flow. In this scenario it is particularly important to study the role of mechanical stress on cancer progression.

Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing.

Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas of young and aged murine mammary tissues. By analyzing epithelial, stromal, and immune cells, we identify age-dependent alterations in cell proportions and gene expression, providing evidence that suggests alveolar maturation and physiological decline.

Enhanced observation time of magneto-optical traps using micro-machined non-evaporable getter pumps.

We show that micro-machined non-evaporable getter pumps (NEGs) can extend the time over which laser cooled atoms can be produced in a magneto-optical trap (MOT), in the absence of other vacuum pumping mechanisms. In a first study, we incorporate a silicon-glass microfabricated ultra-high vacuum (UHV) cell with silicon etched NEG cavities and alumino-silicate glass (ASG) windows and demonstrate the observation of a repeatedly-loading MOT over a 10 min period with a single laser-activated NEG. In a second study, the capacity of passive pumping with laser activated NEG materials is further investigated in a borosilicate glass-blown cuvette cell containing five NEG tablets.

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress.

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis.

Photodynamic Therapy in a 3D Model of Ovarian Cancer.

Photodynamic therapy (PDT), is a clinically-approved light-based anti-cancer treatment modality in which a photoactivatable photosensitizer is irradiated with an appropriate wavelength of light to generate cytotoxic molecules to kill cancer cells. In this article, we describe an PDT protocol using a 3-dimensional (3D) model of ovarian cancer that was established on beds of Matrigel. PDT was performed using a liposomal formulation of verteporfin photosensitizer (Visudyne).

Radiation Therapy Workflow and Dosimetric Analysis from a Phase 1/2 Trial of Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

Purpose: A prospective phase 1/2 trial for electrophysiologic guided noninvasive cardiac radioablation treatment of ventricular tachycardia (ENCORE-VT) demonstrating efficacy for arrhythmia control has recently been reported. The treatment workflow, report dose-volume metrics, and overall process improvements are described here.

Methods And Materials: Patients receiving 25 Gy in a single fraction to the cardiac ventricular tachycardia substrate (identified on presimulation multimodality imaging) on the phase 1/2 trial were included for analysis.

Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia.

Background: Case studies have suggested the efficacy of catheter-free, electrophysiology-guided noninvasive cardiac radioablation for ventricular tachycardia (VT) using stereotactic body radiation therapy, although prospective data are lacking.

Methods: We conducted a prospective phase I/II trial of noninvasive cardiac radioablation in adults with treatment-refractory episodes of VT or cardiomyopathy related to premature ventricular contractions (PVCs). Arrhythmogenic scar regions were targeted by combining noninvasive anatomic and electric cardiac imaging with a standard stereotactic body radiation therapy workflow followed by delivery of a single fraction of 25 Gy to the target.

A Combination of Visudyne and a Lipid-anchored Liposomal Formulation of Benzoporphyrin Derivative Enhances Photodynamic Therapy Efficacy in a 3D Model for Ovarian Cancer.

A major objective in developing new treatment approaches for lethal tumors is to reduce toxicity to normal tissues while maintaining therapeutic efficacy. Photodynamic therapy (PDT) provides a mechanistically distinct approach to treat tumors without the systemic toxicity of chemotherapy drugs. PDT involves the light-based activation of a small molecule, a photosensitizer (PS), to generate reactive molecular species (RMS) that are toxic to target tissue.

Frontal Sinus Development and Juvenile Age Estimation.

Assessment of development is an important component of age estimation in juveniles. One area that has not been fully investigated as a possible aging method is the development of the frontal sinus. The frontal sinuses form when the ectocranial table of the frontal bone separates from the endocranial table forming an air pocket in the bone.

A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease.

Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice.

Forbidden atomic transitions driven by an intensity-modulated laser trap.

Spectroscopy is an essential tool in understanding and manipulating quantum systems, such as atoms and molecules. The model describing spectroscopy includes the multipole-field interaction, which leads to established spectroscopic selection rules, and an interaction that is quadratic in the field, which is not often employed. However, spectroscopy using the quadratic (ponderomotive) interaction promises two significant advantages over spectroscopy using the multipole-field interaction: flexible transition rules and vastly improved spatial addressability of the quantum system.