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The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel ® macrocarriers in fixed-bed BioBLU ® 320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cohen, Simon, Hazan, Tal, Tzadok, Levin, Girshengorn, Mimran, Natan, Baruhi, David, Rosen, Shmaya, Borni, Cohen, Lupu, Kedmi, Zilberman, Jayson, Monash, Dor, Diamant, Goldvaser, Cohen-Gihon, Israeli, Lazar, Shifman, Beth-Din, Zvi, Oren, Makovitzki, Lerer, Mimran, Toister, Zichel, Adar and Epstein.)

Measurements and different analyses of dental casts are essential for precise diagnosis of an orthodontic case. At present, virtual computerized models, such as OrthoCAD, are available for clinicians, supplemented by dedicated software for performing needed measurements on them. The purpose of this study was to test the accuracy of measuring casts with the aid of calipers or OrthoCAD and compare these two techniques. Twenty setups using artificial teeth corresponding to various malocclusions were created. Impressions were taken of them, providing 20 plaster and 20 virtual orthodontic models. Measurements of mesiodistal tooth dimension as well as intercanine and intermolar width were made on both. Additionally, values of tooth size were calculated from the isolated artificial teeth removed from the setups and of arch width from the existing setups. The resulting values were compared by the use of nonparametric statistics, and methods' errors were also calculated. Results showed the methods being highly valid and reproducible for both tooth size and arch width. For the tested clinically applicable methods, measurement with digital calipers on plaster models showed the highest accuracy and reproducibility, closely followed by OrthoCAD. Digital calipers seem to be a more suitable instrument for scientific work. However, OrthoCAD's accuracy is clinically acceptable, and most likely, considering its present advantages and future possibilities, the examined or an equivalent 3D virtual models' procedure would become the standard for orthodontic clinical use.

The purpose of this study was to assess the effects of cyclophosphamide on cartilaginous growth and differentiation. Cyclophosphamide is a drug commonly used in the treatment of neoplastic diseases and in preparation for bone marrow transplantation. Eighteen Sprague-Dawley rats divided into control and experimental groups received 2 i.p. injections of either saline or cyclophosphamide (30 mg/kg) with a 3-day interval starting from day 10 after birth. Effects on the proximal femoral epiphyses were evaluated histomorphometrically as well as semi-quantitatively at day 31 after birth. Results showed a significant reduction in length of the cyclophosphamide-treated femora compared to the controls. This could be attributed to a significant reduction in the thickness of the growth zone. Cell differentiation throughout the growth plates was clearly disturbed, involving nesting of cells, loss of polarity, and impaired maturation as seen by areas of excessive hyalinization. Although the effects of cyclophosphamide on the growth plates were significant compared to controls, the changes were not as extensive as previous reports have indicated. This could be attributed primarily to the fact that a comparatively low dose of the drug was used in the present study. Also, a period of recovery was allowed prior to evaluation. Nevertheless, significant effects remained which should be considered when treating young children with cyclophosphamide.