Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice

Sakurai F., Iizuka S., Tsukamoto T., et al. Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice. Journal of Controlled Release 374, 415 (2024); https://doi.org/10.1016/j.jconrel.2024.08.022.Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6–6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice

Atypical ST-Segment-Elevation Myocardial Infarction Presentation in Patients With COVID-19 at a High-Volume Center in New York City

Atypical presentations of ST-segment-elevation myocardial infarction (STEMI) have been reported in patients who have COVID-19. We have seen this occurrence in our center in Bronx, New York, where multitudes of patients sought treatment for the coronavirus. We studied the prevalence of atypical STEMI findings among patients with COVID-19 who presented during the first 2 months of the pandemic. Consistent with previous reports, 4 of our 10 patients with COVID-19 and STEMI had no identifiable culprit coronary lesion; rather, they often had diffuse ST-segment elevations on surface electrocardiograms along with higher levels of D-dimer and inflammatory markers. In contrast, 32 of 33 patients without COVID-19 (97%) had a culprit lesion. The patients with COVID-19 and a culprit lesion more often needed thrombectomy catheterization and administration of glycoprotein IIb/IIIa inhibitors. Our study confirms that patients with COVID-19 often have atypical STEMI presentations, including the frequent absence of a culprit coronary lesion. Our findings can help clinicians prepare for these atypical clinical presentations

Development of a Compact Wide-Field Telescope to be Mounted on VERTECS

In recent years, CubeSat projects have initiated plans to conduct astronomical observations by deploying mission payloads. CubeSats present a promising solution for swiftly addressing critical challenges in astrophysics with flexibility. Within Cubeats, where both the bus system and mission payload occupy about half of the volume, there is a necessity to miniaturize mission equipment. The critical factor in astronomical observations, light-gathering ability, is determined not only by the aperture size but, more importantly for diffuse emission, by the optical throughput, i.e., the product of the aperture area and the observing solid angle. Consequently, even with a compact optical system, specializing in wide-field observations enables achieving light-gathering ability equivalent to that of a large-diameter telescope. Therefore, we propose equipping CubeSats with small, wide-field telescopes specialized for observing essential quantities in understanding the cosmic history of star formation, such as extragalactic background Light (EBL), and foreground components like zodiacal light and diffuse galactic light. Radiation from first-generation celestial bodies, which is challenging to detect due to their darkness in the distant universe, is included in the EBL in the visible to near-infrared wavelengths. Hence, wide-field survey observations in the visible and near-infrared play a crucial role in unraveling when, where, and how the first-generation stars were born in the early universe. However, current technology has not enabled the development of CubeSats with mechanisms capable of cooling infrared detectors to temperatures below a few tens of Kelvin. Therefore, we have designed an optical system focusing on the visible EBL. In the astronomical W6U CubeSat mission VERTECS (Visible Extragalactic background RadiaTion Exploration by CubeSat), we are developing a 3U mission payload, comprised of 1U-sized lens optics, camera modules, and baffles each. The lens optical system achieves a high throughput ( \u3e 10-6 m2 sr) by covering the entire field of view with 6 degrees by 6 degrees and each pixel with a field of view of 11 arcseconds by 11 arcseconds. The camera module uses a CMOS sensor with high quantum efficiency in visible light, featuring sufficiently low dark current noise (approximately 0.01 electrons per second at 269 K) and readout noise (approximately 2.6 electrons at 24 dB analog gain), compared to the photocurrent generated by the EBL and foreground photon noise. The baffle is designed to attenuate stray light from the Sun and Earth to negligible levels compared to the EBL signal. Additionally, a set of color filters divides the wavelength range of 400 to 800 nm into four bands. In our observation strategy, we capture 60-second exposure images by shifting the field of view by 3 degrees and perform photometry on the stacked images in the four bands. VERTECS project was selected in JAXA-Small Satellite Rush Program in 2022 and is currently advancing in satellite development, with a scheduled launch in FY2025. Thus far, a significant portion of the mission payload design meets the required specifications, and progress is underway towards the fabrication of the engineering model. In this presentation, we will report on the progress of our optical telescope development, our strategy for visible EBL observations, and our future plans

Dual-Antiplatelet Therapy Cessation and Cardiovascular Risk in Relation to Age: Analysis From the PARIS Registry.

OBJECTIVES: The aim of this study was to examine the association between dual-antiplatelet therapy (DAPT) cessation and cardiovascular risk after percutaneous coronary intervention in relation to age. BACKGROUND: Examination of outcomes by age after percutaneous coronary intervention is relevant given the aging population. METHODS: Two-year clinical outcomes, incidence, and effect of DAPT cessation on outcomes were compared by ages ≤55, 56 to 74, and ≥75 years from the PARIS (Patterns of Non-Adherence to Antiplatelet Regimens in Stented Patients) registry. DAPT cessation included physician-recommended discontinuation, interruption for surgery, and disruption (from noncompliance or bleeding). Clinical endpoints were major adverse cardiac events (MACE) (a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, or clinically indicated target lesion revascularization), a secondary restrictive definition of MACE (MACE2) excluding target lesion revascularization, and bleeding. RESULTS: A total of 1,192 patients (24%) were ≤55 years, 2,869 (57%) were 56 to 74 years, and 957 (19%) were ≥75 years of age. Patients ≥75 years of age had higher DAPT cessation rates and increased risk for MACE2, death, cardiac death, and bleeding compared with younger patients. Discontinuation and interruption were not associated with increased cardiovascular risk across age groups, whereas disruption was associated with increased risk for MACE and MACE2 in younger patients but not in patients ≥75 years of age (p for trend <0.05). CONCLUSIONS: Nonadherence and outcomes vary by age, with patients ≥75 years having the highest DAPT cessation rates. We observed no association between outcomes and DAPT cessation in patients ≥75 years, whereas discontinuation was associated with lower MACE rates and disruption with increased MACE rates in patients <75 years

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria

The version of record of this article, first published in Gastric Cancer, is available online at Publisher’s website: https://doi.org/10.1007/s10120-024-01511-8.Background: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. Methods: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. Results: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76–0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70–0.85) (P = 0.006, DeLong’s test). Conclusions: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. Mini-abstract: We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria

VERTECS: 6U CubeSat Mission to Study Star-Formation History by Observation of Visible Extragalactic Background Light

We describe an astronomical 6U CubeSat mission VERTECS (Visible Extragalactic background RadiaTion Exploration by CubeSat). The scientific purpose of VERTECS is to reveal star-formation history of the universe by observation of the extragalactic background light (EBL) in visible wavelengths. Earlier observations by sounding rockets and infrared astronomical satellites have shown that the near-infrared EBL is several times brighter than the integrated light of known galaxies. As candidates for the excess light, first-generation stars in the early universe or low-redshift intra-halo light have been proposed, but it has not been concluded. Since these objects are expected to show different emission spectra in visible wavelengths, precise visible observation is important to reveal the origin of excess light. Since detection sensitivity of the EBL is determined by the product of telescope aperture and field of view, a small wide-field telescope system enables the EBL observation with high sensitivity. In VERTECS mission, we develop a 6U CubeSat equipped with a 3U size telescope optimized for observation of visible EBL. The telescope is composed of lens optics and a CMOS sensor of 3k times 3k array format, which is designed to observe the sky in four photometric bands in 400-800nm. The satellite bus is composed of on-board computer (OBC), electric power system (EPS), communication (COM), attitude determination and control system (ACDS), and thermal structure. Design of OBC and EPS is based on heritage of CubeSats developed at Kyushu Institute of Technology, but deployable solar array wings is added to EPS to supply sufficient power to the VERTECS subsystems. In COM system, S-band is used for command uplink and X-band is used for high-speed downlink of large-size images captured by the telescope. Since the EBL measurement need discrimination of the background light from discrete foreground stars, VERTECS requires 10 arcseconds pointing stability (1 sigma) over 1 minute exposure. In 2022, VERTECS was selected for JAXA-Small Satellite Rush Program (JAXA-SMASH Program), a new program that encourages universities, private companies and JAXA to collaborate to realize small satellite missions utilizing commercial small launch opportunities, and to diversify transportation services in Japan. We have been working on functionality and interface teast using Bread Board Model (BBM), and enviroonmental tests by using the satellite structure thermal model. Launch of the satellite is planned in FY2025. We aim at developing the satellite and obtaining scientific results much more quickly than recent large astronomical-satellite missions

A powered simple walking model explains the decline in propulsive force and hip flexion torque compensation in human gait

Abstract Excessive hip flexion torque to prioritize leg swings in the elderly is likely to be a factor that reduces their propulsive force and gait stability, but the mechanism is not clear. To understand the mechanism, we investigated how propulsive force, hip flexion torque, and margin of stability (MoS) change when only the hip spring stiffness is increased without changing the walking speed in the simple walking model, and verified whether the relationship holds in human walking. The results showed that at walking speeds between 0.50 and 1.75 m/s, increasing hip spring stiffness increased hip flexion torque and decreased the propulsive force and MoS in both the model and human walking. Furthermore, it was found that the increase in hip flexion torque was explained by the increase in spring stiffness, and the decreases in the propulsive force and MoS were explained by the increase in step frequency associated with the increase in spring stiffness. Therefore, the increase in hip flexion torque likely decreased the propulsive force and MoS, and this mechanism was explained by the intervening hip spring stiffness. Our findings may help in the control design of walking assistance devices, and in improving our understanding of elderly walking strategies