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We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects (n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (-0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung.NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.

PurposeTo accurately and efficiently reconstruct a continuous surface from noisy point clouds captured by a surface photogrammetry system (VisionRT).MethodsThe authors have developed a level-set based surface reconstruction method on point clouds captured by a surface photogrammetry system (VisionRT). The proposed method reconstructs an implicit and continuous representation of the underlying patient surface by optimizing a regularized fitting energy, offering extra robustness to noise and missing measurements. By contrast to explicit/discrete meshing-type schemes, their continuous representation is particularly advantageous for subsequent surface registration and motion tracking by eliminating the need for maintaining explicit point correspondences as in discrete models. The authors solve the proposed method with an efficient narrowband evolving scheme. The authors evaluated the proposed method on both phantom and human subject data with two sets of complementary experiments. In the first set of experiment, the authors generated a series of surfaces each with different black patches placed on one chest phantom. The resulting VisionRT measurements from the patched area had different degree of noise and missing levels, since VisionRT has difficulties in detecting dark surfaces. The authors applied the proposed method to point clouds acquired under these different configurations, and quantitatively evaluated reconstructed surfaces by comparing against a high-quality reference surface with respect to root mean squared error (RMSE). In the second set of experiment, the authors applied their method to 100 clinical point clouds acquired from one human subject. In the absence of ground-truth, the authors qualitatively validated reconstructed surfaces by comparing the local geometry, specifically mean curvature distributions, against that of the surface extracted from a high-quality CT obtained from the same patient.ResultsOn phantom point clouds, their method achieved submillimeter reconstruction RMSE under different configurations, demonstrating quantitatively the faith of the proposed method in preserving local structural properties of the underlying surface in the presence of noise and missing measurements, and its robustness toward variations of such characteristics. On point clouds from the human subject, the proposed method successfully reconstructed all patient surfaces, filling regions where raw point coordinate readings were missing. Within two comparable regions of interest in the chest area, similar mean curvature distributions were acquired from both their reconstructed surface and CT surface, with mean and standard deviation of (μrecon=-2.7×10(-3) mm(-1), σrecon=7.0×10(-3) mm(-1)) and (μCT=-2.5×10(-3) mm(-1), σCT=5.3×10(-3) mm(-1)), respectively. The agreement of local geometry properties between the reconstructed surfaces and the CT surface demonstrated the ability of the proposed method in faithfully representing the underlying patient surface.ConclusionsThe authors have integrated and developed an accurate level-set based continuous surface reconstruction method on point clouds acquired by a 3D surface photogrammetry system. The proposed method has generated a continuous representation of the underlying phantom and patient surfaces with good robustness against noise and missing measurements. It serves as an important first step for further development of motion tracking methods during radiotherapy.

The photoinduced crawling motion of crystals is a continuous motion that azobenzene molecular crystals exhibit under light irradiation. Such motion enables object manipulation at the microscale with a simple setup of fixed LED light sources. Transportation of nano-/micromaterials using photoinduced crawling motion has recently been reported. However, the details of the motion mechanism have not been revealed so far. Herein, we report visualization of the dynamics of fine particles in 4-(methylamino)azobenzene (4-MAAB) crystals under light irradiation via diffracted X-ray tracking (DXT). Continuously repeated melting and recrystallization of 4-MAAB crystals under light irradiation results in the flow of liquid 4-MAAB. Zinc oxide (ZnO) particles were introduced inside the 4-MAAB crystals to detect diffracted X-rays. The ZnO particles rotate with the flow of liquid 4-MAAB. By using white X-rays with a wide energy width, the rotation of each zinc oxide nanoparticle was detected as the movement of a bright spot in the X-ray diffraction pattern. It was clearly shown that the ZnO particles rotated increasingly as the irradiation light intensity increased. Furthermore, we also found anisotropy in the rotational direction of ZnO particles that occurred during the crawling motion of 4-MAAB crystals. It has become clear that the flow perpendicular to the supporting film of 4-MAAB crystals is enhanced inside the crystal during the crawling motion. DXT provides a unique means to elucidate the mechanism of photoinduced crawling motion of crystals. [ABSTRACT FROM AUTHOR]

X-ray crystallography has revolutionized our understanding of biological macromolecules by elucidating their three-dimensional structures. However, the use of X-rays in this technique raises concerns about potential damage to the protein crystals, which results in a quality degradation of the diffraction data even at very low temperatures. Since such damage can occur on the micro- to millisecond timescale, a development in its real-time measurement has been expected. Here, we introduce diffracted X-ray blinking (DXB), which was originally proposed as a method to analyze the intensity fluctuations of diffraction of crystalline particles, to small-angle X-ray scattering (SAXS) of a lysozyme single-crystal. This novel technique, called the small-angle X-ray blinking (SAXB) method, analyzes the fluctuation in SAXS intensity reflecting the domain fluctuation in the protein crystal caused by the X-ray irradiation, which could be correlated with the X-ray-induced damage on the crystal. There was no change in the protein crystal's domain dynamics between the first and second X-ray exposures at 95K, each of which lasted 0.7 s. On the other hand, its dynamics at 295K increased remarkably. The SAXB method further showed a dramatic increase in domain fluctuations with an increasing dose of X-ray radiation, indicating the significance of this method. [ABSTRACT FROM AUTHOR]

Dynamic behavior in soft matter physics, biology, and nanoscience frequently occurs on submicrosecond timescales. Diffracted x-ray blinking (DXB) is a unique method that can provide a broad range of spatial scale information and is becoming an attractive tool for use at high repetition rate x-ray facilities. In this study, we performed DXB experiments with 890 ns time resolution at the European X-ray Free-Electron Laser Facility to obtain dynamic information about rubber samples that are typically used in automobile tires. Time-resolved scattering was simultaneously recorded for two samples that mainly consisted of carbon black (CB) and polybutadiene (PB). These samples contained either graphitized or non-graphitized CB and displayed significantly different dynamics. A clear interaction between CB and PB was observed, indicating that the mobility of PB was changed by the introduction of CB. Restricted polymer motion was observed in the q-range of 0.78–1.58 Å−1 regions. Our results suggest that the particle network can be flexibly controlled without impairing the mechanical strength of the rubber. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non‐dependent regions, which are potentially vulnerable to increased mechanical stress and injury?What is the main finding and its importance?Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non‐dependent regions, potentially protecting them from overinflation and injury. Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non‐dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (−1.6 ± 0.3 cmH2O highly inflated; −1.4 ± 0.3 cmH2O intermediate; −1.1 ± 0.1 cmH2O normally inflated; P = 0.05) but not while prone (−1.4 ± 0.2 cmH2O highly inflated; −1.3 ± 0.2 cmH2O intermediate; −1.3 ± 0.1 cmH2O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (−0.24 ± 0.02 cmH2O/cm supine; −0.18 ± 0.04 cmH2O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P < 0.0001), was greater in the supine posture than when prone (−0.57 ± 0.21 cmH2O/cm supine; −0.34 ± 0.16 cmH2O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (−0.51 cmH2O/cm). The non‐dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12–20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy. [ABSTRACT FROM AUTHOR]

Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, using a mouse model of obesity-induced hepatocellular carcinoma (HCC), we identified the release mechanism of SASP factors, which include interleukin-1β (IL-1β)– and IL-1β–dependent IL-33, from senescent hepatic stellate cells (HSCs) via gasdermin D (GSDMD) amino-terminal–mediated pore. We found that IL-33 was highly induced in senescent HSCs in an IL-1β–dependent manner in the tumor microenvironment. The release of both IL-33 and IL-1β was triggered by lipoteichoic acid (LTA), a cell wall component of gut microbiota that was transferred and accumulated in the liver tissue of high-fat diet–fed mice, and the release of these factors was mediated through cell membrane pores formed by the GSDMD amino terminus, which was cleaved by LTA-induced caspase-11. We demonstrated that IL-33 release from HSCs promoted HCC development via the activation of ST2-positive Treg cells in the liver tumor microenvironment. The accumulation of GSDMD amino terminus was also detected in HSCs from human NASH-associated HCC patients, suggesting that similar mechanism could be involved in a certain type of human HCC. These results uncover a release mechanism for SASP factors from sensitized senescent HSCs in the tumor microenvironment, thereby facilitating obesity-associated HCC progression. Furthermore, our findings highlight the therapeutic potential of inhibitors of GSDMD-mediated pore formation for HCC treatment. Release of IL-33 in HCC: Secretion of senescence-associated secretory phenotype (SASP) factors by senescent hepatic stellate cells promotes the development of hepatocellular carcinoma (HCC); however, the release mechanism is not well understood. Yamagishi et al. used an obesity-induced HCC mouse model to study SASP factor release from hepatic stellate cells within tumors. IL-33 release was triggered by lipoteichoic acid, which accumulated in the livers of obese mice. Full-length IL-33 was cleaved to its short active form and released into the tumor microenvironment through gasdermin D N-terminal pores. Secreted IL-33 bound to ST2+ Treg cells, resulting in impaired CD8+-mediated antitumor immunity and the development of HCC. These findings shed light on SASP factor release and suggest that targeting IL-33 release from senescent cells may be an attractive therapy for HCC. [ABSTRACT FROM AUTHOR]

Purpose: To develop a noninvasive prognostic imaging biomarker related to hypoxia to predict SABR tumor control.Methods and Materials: A total of 145 subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using cone beam computed tomography guidance on a small animal irradiator at 225 kV. Various doses in the range of 0 to 100 Gy were administered, while rats breathed air or oxygen, and tumor control was assessed up to 200 days. Oxygen-sensitive magnetic resonance imaging (MRI) (T1-weighted, ΔR1, ΔR2*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia.Results: Increasing radiation dose in the range of 0 to 90 Gy enhanced tumor control of air-breathing rats with a TCD50 estimated at 59.6 ± 1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (eg, 40 Gy; P < .05), and overall there was a modest left shift in the control curve: TCD50(oxygen) = 53.1 ± 3.1 Gy (P < .05 vs air). Oxygen-sensitive MRI showed variable response to oxygen gas breathing challenge; the magnitude of T1-weighted signal response (%ΔSI) allowed stratification of tumors in terms of local control at 40 Gy. Tumors showing %ΔSI >0.922 with O2-gas breathing challenge showed significantly better control at 40 Gy during irradiation while breathing oxygen (75% vs 0%, P < .01). In addition, increased radiation dose (50 Gy) substantially overcame resistance, with 50% control for poorly oxygenated tumors. Stratification of dose-response curves based on %ΔSI >0.922 revealed different survival curves, with TCD50 = 36.2 ± 3.2 Gy for tumors responsive to oxygen gas breathing challenge; this was significantly less than the 54.7 ± 2.4 Gy for unresponsive tumors (P < .005), irrespective of the gas inhaled during tumor irradiation.Conclusions: Oxygen-sensitive MRI allowed stratification of tumors in terms of local control at 40 Gy, indicating its use as a potential predictive imaging biomarker. Increasing dose to 50 Gy overcame radiation resistance attributable to hypoxia in 50% of tumors. [ABSTRACT FROM AUTHOR]

In recent years, real-time observations of molecules have been required to understand their behavior and function. To date, we have reported two different time-resolved observation methods: diffracted x-ray tracking and diffracted x-ray blinking (DXB). The former monitors the motion of diffracted spots derived from nanocrystals labeled onto target molecules, and the latter measures the fluctuation of the diffraction intensity that is highly correlated with the target molecular motion. However, these reports use a synchrotron x-ray source because of its high average flux, resulting in a high time resolution. Here, we used a laboratory x-ray source and DXB to measure the internal molecular dynamics of three different systems. The samples studied were bovine serum albumin (BSA) pinned onto a substrate, antifreeze protein (AFP) crystallized as a single crystal, and poly{2-(perfluorooctyl)ethyl acrylate} (PC8FA) polymer between polyimide sheets. It was found that not only BSA but also AFP and PC8FA molecules move in the systems. In addition, the molecular motion of AFP molecules was observed to increase with decreasing temperature. The rotational diffusion coefficients (DR) of BSA, AFP, and PC8FA were estimated to be 0.73 pm2/s, 0.65 pm2/s, and 3.29 pm2/s, respectively. Surprisingly, the DR of the PC8FA polymer was found to be the highest among the three samples. This is the first report that measures the molecular motion of a single protein crystal and polymer by using DXB with a laboratory x-ray source. This technique can be applied to any kind of crystal and crystalline polymer and provides atomic-order molecular information. [ABSTRACT FROM AUTHOR]

Introduction: We previously introduced the inverse solution guidance algorithm (ISGA) methodology using a Single Equivalent Moving Dipole model of cardiac electrical activity to localize both the exit site of a re‐entrant circuit and the tip of a radiofrequency (RF) ablation catheter. The purpose of this study was to investigate the use of ISGA for ablation catheter guidance in an animal model. Methods: Ventricular tachycardia (VT) was simulated by rapid ventricular pacing at a target site in eleven Yorkshire swine. The ablation target was established using three different techniques: a pacing lead placed into the ventricular wall at the mid‐myocardial level (Type‐1), an intracardiac mapping catheter (Type‐2), and an RF ablation catheter placed at a random position on the endocardial surface (Type‐3). In each experiment, one operator placed the catheter/pacing lead at the target location, while another used the ISGA system to manipulate the RF ablation catheter starting from a random ventricular location to locate the target. Results: The average localization error of the RF ablation catheter tip was 0.31 ± 0.08 cm. After analyzing approximately 35 cardiac cycles of simulated VT, the ISGA system's accuracy in locating the target was 0.4 cm after four catheter movements in the Type‐1 experiment, 0.48 cm after six movements in the Type‐2 experiment, and 0.67 cm after seven movements in the Type‐3 experiment. Conclusion: We demonstrated the feasibility of using the ISGA method to guide an ablation catheter to the origin of a VT focus by analyzing a few beats of body surface potentials without electro‐anatomic mapping. [ABSTRACT FROM AUTHOR]

Captions, which are used as a means of information support for deaf and hard-of-hearing students, are usually presented only in text form. Therefore, when mathematical equations and figures are frequently used in a classroom, the captions will show several demonstrative words such as "this equation" or "that figure." As there is a delay between the teacher's utterance and the display of the captions sometimes, it is difficult for users to grasp the target of these demonstrative words accurately. In this study, we prepared hybrid captions with mathematical equations and figures and verified their effectiveness via a comparison with conventional text-only captions. The results suggested that the hybrid captions were at least as effective as the conventional captions at helping the students understand the lesson contents. A subjective evaluation with a questionnaire survey also showed that the experimental participants found the hybrid captions to be acceptable without any discomfort. Furthermore, there was no difference in the number of eye movements of the participants during the experiment, suggesting that the physical load was similar for both types of captions. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumonia with mild CNS involvements should be considered of MERS, even in adult. From the case series, splenial single lesions by MRI and prodromal fever with varied neurological manifestations recovered completely by antibiotics were seen. [ABSTRACT FROM AUTHOR]