Electrical Engineering and Computer Science

PurposeEarly detection of right ventricular (RV) dysfunction is essential in pulmonary arterial hypertension (PAH) but remains challenging using conventional echocardiography. This study investigates the feasibility of a noninvasive, physics-based framework using three-dimensional (3D) echocardiography that integrates myocardial strain and volumetric flow analysis to characterize RV mechanical performance across stages of PAH.MethodsA prospective pilot study (N = 15) enrolled healthy controls, PAH patients with preserved RV size, and PAH patients with RV dysfunction. Deformation was evaluated by principal strain analysis and by conventional (longitudinal, circumferential) components. Hemodynamic metrics included hemodynamic forces and energetic properties that were derived using a physics-informed volumetric echocardiographic particle image velocimetry (V-Echo-PIV) method applied to contrast-enhanced acquisitions.ResultsDeformation analysis revealed that longitudinal strain was significantly reduced even in PAH patients with preserved RV dimensions, while second principal (secondary) strain showed a distinctive sign reversal, indicating a paradoxical systolic lengthening, early in the disease. The analysis of hemodynamic forces showed a marked reduction in systolic propulsion across all PAH stages. In contrast, energetic abnormalities were predominantly observed at later stage of the disease.ConclusionsThe integration of 3D myocardial strain with fluid dynamics provides a comprehensive physiological assessment of RV remodeling. While strain and systolic propulsion appear as sensitive markers for early dysfunction, diastolic energetics may support disease staging. This noninvasive framework shows promise for early detection and longitudinal monitoring of PAH patients.

Mitochondrial transplantation has emerged as a promising cardioprotective strategy for ischemia-reperfusion injury, aiming to restore bioenergetic function by delivering healthy mitochondria to damaged tissue. However, conflicting reports exist regarding whether mitochondria can survive exposure to the calcium-rich extracellular environment, such as the bloodstream, prior to cellular uptake. Resolving this question is essential for advancing the therapeutic use of mitochondria in clinical settings. Isolated mitochondria from L6 rat skeletal muscle cells were incubated with physiologic (1.3  mM), sub-physiologic (0.65  mM), and supraphysiologic (2.6  mM) concentrations of calcium. Mitochondrial membrane potential was assessed using MitoTracker™ Red FM fluorescence, and structural integrity was evaluated using impedance-based Coulter counter analysis over a 12-hour time course. Mitochondria exposed to 1.3  mM calcium retained 90-95 % membrane potential by 12 h, while 2.6  mM calcium caused progressive loss of function and integrity, approaching levels seen in freeze-thawed controls. Coulter counter measurements revealed more extensive mitochondrial loss across all calcium-treated groups than fluorescence assays alone, suggesting that dye-based methods may underestimate structural damage. Nonetheless, a substantial proportion of mitochondria remained both structurally and functionally intact at physiologically relevant calcium levels. These findings demonstrate that a substantial number of mitochondria can retain membrane potential and structural integrity after exposure to extracellular calcium concentrations approximating those found in blood. This supports the feasibility of intracoronary mitochondrial transplantation and underscores the need for further in vivo studies to optimize survival and efficacy of mitochondria delivered in calcium-rich environments.

PURPOSE: To evaluate changes in myocardial blood flow (MBF) and coronary flow reserve (CFR) over time in a swine model fed a Western diet (WD) using a novel low-dose myocardial CT perfusion technique. MATERIALS AND METHODS: Ten swine with low-density lipoprotein receptor mutations were fed a WD starting at week 0 and imaged after 12, 16, 17, 18, 19, or 23 weeks of WD exposure (mean ± SD: 17.1 ± 3.25 weeks; range 12-23 weeks) using a 320-slice CT scanner under rest and adenosine-induced stress (240 μg/kg/min). Peripheral contrast injection (370 mgI/mL, 0.5 mL/kg, 5 mL/s) with a diluted chaser (30:70 contrast/saline) was followed by bolus tracking and a single-volume scan acquired at peak aortic enhancement (100 kVp, 200 mA). A first-pass analysis model derived MBF (mL/min/g) from bolus-tracking and scan data. Rest and stress MBF were used to compute CFR. Correlations between WD duration and both stress MBF and CFR were assessed. Reproducibility was evaluated through paired repeated scans. The CT dose index was recorded. RESULTS: Starting at 12 weeks post-WD, stress-induced MBF and CFR were strongly correlated with WD duration: MBFstress = -0.05 T + 2.56 (r = -0.93) and CFR = -0.13 T + 4.30 (r = -0.76). Reproducibility between repeated MBF measurements was high (MBF2 = 0.97MBF1 + 0.05; r = 0.99; RMSE = 0.06 mL/min/g). The average CT dose index was 7.4 mGy. CONCLUSION: Prolonged Western diet consumption in this swine model was associated with a progressive decline in stress-induced MBF and CFR, indicating the development of diet-related myocardial microvascular dysfunction. These results suggest that the low-dose single-volume CT perfusion technique can detect early perfusion impairments before overt disease, offering a promising tool for early risk stratification in coronary artery disease. SUMMARY STATEMENT: A novel low-dose, single-volume CT perfusion technique enables early detection of coronary microvascular dysfunction associated with Western diet exposure, providing a non-invasive and radiation-efficient method for assessing myocardial blood flow and coronary flow reserve before the development of significant epicardial stenosis.

Purpose of ReviewTo provide the most up-to-date clinical evidence of intracoronary optical coherence tomography (OCT), and clinical implications to guide future imaging research in cardiology.Recent FindingsIntracoronary OCT has demonstrated advanced system performance and high reproducibility in analyzing atherosclerotic lesions. It is an attractive tool due to its capability for functional classification and superior imaging resolution, enabling precise and reliable tissue assessments. Compared to traditional angiography, OCT has been associated with improved long-term clinical outcomes and serves as an effective tool for optimizing stent selection and post-intervention evaluation. The development of OCT variations and the combination of various intravascular imaging modalities further enhance its diagnostic capabilities, allowing a comprehensive assessment of complex vulnerable lesions and improving risk stratification for patients. SummaryCurrent and evolving system development presents a hopeful path for treating coronary artery disease by addressing the challenges of the intracoronary OCT technique. Future studies focusing on utilizing OCT system extensions, integrated multimodality imaging systems, and Artificial Intelligence (AI) derived image analysis will improve clinical endpoints and streamline the process.

CXL shared memory and persistent memory allow the contents of memory to persist beyond crashes. Stores to persistent or CXL memory are typically not immediately made persistent; developers must manually flush the corresponding cache lines to force the data to be written to the underlying storage. Correctly using flush and fence operations is known to be challenging. While state-of-the-art tools can find missing flush instructions, they often require bug-revealing test cases. No existing tools can ensure the absence of missing flush bugs. In this paper, we present PMRobust, a compiler that automatically inserts flush and fence operations to ensure that code using persistent memory is free from missing flush and fence bugs. PMRobust employs a novel static analysis with optimizations that target newly allocated objects. We have evaluated PMRobust on persistent memory libraries and several persistent memory data structures and measured a geometric mean overhead of 0.26% relative to the original benchmarks with hand-placed flush and fence operations.

Abstract

We implement a paraxial azimuthally-radially polarized beam (ARPB), a novel class of structured light beams that can be optimal chiral (OC), leading to maximum chirality density at a given energy density. By using vectorial light shaping techniques, we successfully generated a paraxial ARPB with precise control over its features, validating theoretical predictions. Our findings demonstrate the ability to finely adjust the chirality density of the ARPB across its entire range by manipulating a single beam parameter. Although our experimental investigations are primarily focused on the transverse plane, we show that fields whose transverse components satisfy the optimal chirality condition are optimally chiral in all directions, and our results highlight the promising potential of OC structured light for applications in the sensing and manipulation of chiral particles. We show that helicity density is more general than the concept of handedness. This work represents a significant advancement toward practical optical enantioseparation and enantiomer detection at the nanoscale.

Compute Express Link (CXL) memory sharing, persistent memory, and other related technologies allow data to survive crash events. A key challenge is ensuring that data is consistent after crashes such that it can be safely accessed. While there has been much work on bug-finding tools for persistent memory programs, these tools cannot guarantee that a program is crash-consistent. In this paper, we present a language, CrashLang, and its type system, that together guarantee that well-typed data structure implementations written in CrashLang are crash-consistent. CrashLang leverages the well-known commit-store pattern in which a single store logically commits an entire data structure operation. In this paper, we prove that well-typed CrashLang programs are crash-consistent, and provide a prototype implementation of the CrashLang compiler. We have evaluated CrashLang on five benchmarks: the Harris linked list, the Treiber stack, the Michael–Scott queue, a Read-Copy-Update binary search tree, and a Cache-Line Hash Table. We experimentally verified that each implementation correctly survives crashes.

Neuropathic pain is a devastating experience for patients and its treatment remains challenging. Dorsal root ganglion (DRG) is currently an important therapeutic target and DRG-targeted analgesic delivery through systemic injection is however not reported. Herein, a disintegrin and metalloproteinase protein 8 (ADAM8), a membrane-anchored protein primarily recognized as a cancer biomarker, is found to be de novo and persistently upregulated in the DRG neurons in spared nerve injury (SNI) and chemotherapy-induced neuropathic pain (CINP), two neuropathic pain models with distinct mechanisms. We thus designed a DRG-targeted delivery strategy using lipid nanoparticles (LNPs), aiming to effectively deliver conventional analgesics to the DRG to improve analgesic effect through blocking pain signal transduction from the periphery to central nervous system. In vitro and in vivo results revealed that LNPs extended the duration of action of the free analgesic from less than 6 h to more than 24 h and particularly, showed therapeutic superiority over conventional liposomes, achieved by their good structural stability for a more sustained release kinetics. After functionalized with a specific ADAM8 inhibitory peptide, the intravenously injected LNPs facilitated analgesic accumulation in the DRG in SNI and CINP. As a result, the LNPs significantly improved the intensity of action for pain relief in a single or repeated treatments, which ultimately relieved pain-related psychiatric comorbidities, while not causing latent systemic toxicities. To our best knowledge, it is the first example of nanoparticles-based DRG-targeted delivery strategy through systemic injection in treating neuropathic pain.

The sclera, the eye's primary load-bearing tissue, substantially influences the globe's response to intraocular pressure. Although the mechanical properties of the anterior and posterior segments have been extensively studied, the equatorial sclera's properties remain underexplored, limiting our understanding of ocular conditions like myopia, ocular trauma, and glaucoma. Traditional studies that rely solely on fiber orientation to explain scleral mechanics may overlook the tissue's complex biomechanical behavior. To address this gap, we conducted a comprehensive investigation using ultrasonic elastography, optical coherence elastography, and polarizing light microscopy to analyze the equatorial sclera's anisotropic properties. Our findings reveal a counterintuitive result: Mechanical anisotropy in the equatorial sclera contradicts preferred fiber orientation. This integrated approach not only challenges prevailing models of scleral biomechanics but also provides fundamental insights into the mechanisms underlying key ocular conditions, highlighting the importance of multimodal and multiscale analyses in biological tissue research.