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  • 1
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 12 ( 2024-2-21)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2719493-0
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  • 2
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 7 ( 2019-8-7)
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2711999-3
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  • 3
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 14 ( 2023-3-7)
    Abstract: In August 2020 during Israel’s second COVID-19 wave Rambam Medical Center opened the Sammy Ofer Fortified Underground Emergency Hospital. This was declared a regional Corona center in the north of Israel, receiving the most severe Corona patients from the region. Alongside the advanced inpatient capacity and technology within the underground facility, there was a severe shortage of trained medical and paramedical staff, as well as harsh working conditions. The current study examined the implications and effects of working in an underground facility on healthcare workers, focusing on emotion regulation tendencies and profession as predictors of job burnout. Methods Seventy-six healthcare workers, who had worked in the underground hospital for a minimum continuous period of 2 weeks during the peak of the COVID-19 pandemic, and a control group of 40 healthcare workers from northern Israel were asked to fill out an online survey administered via Qualtrics (total sample 116). The survey comprised six questionnaires: a demographic survey questionnaire; a COVID-19 concerns questionnaire; a psychological distress questionnaire (DASS, Depression Anxiety Stress Scale); trait worry (PSWQ; Penn State Worry Questionnaire); emotion regulation (ERQ, Emotion Regulation Questionnaire), and burnout (SMBM, Shirom - Melamed Burnout Measure). Results Independent-samples t -tests revealed no significant differences in psychological distress or burnout between Rambam Underground hospital workers and the control group. Conversely, COVID-19 concern scores were significantly different in the two groups, the Rambam hospital workers showing less concern ( M = 2.9 , SD = 0.73) than the control group ( M = 3.47 , SD = 0.76) [ t (114) = −3.974, p & lt; 0.001]. Hierarchical linear regression analysis identified the significant predictors of burnout among healthcare workers. Participants’ profession (physician), psychological distress (total DASS score), and a personality trait of worry were statistically significant predictors for job burnout ( p = 0.028, p & lt; 0.001, p = 0.023, respectively). Concerns about COVID-19 marginally predicted job burnout ( p = 0.09). Group (underground vs. control) and emotion regulation tendencies did not predict burnout. Conclusion The two groups showed no significant differences in psychological distress nor in burnout. Being a physician, having an intrinsic trait of being overly worried and experiencing psychological distress were significant predictors for job burnout among healthcare workers, regardless of work environment (underground vs. control).
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564218-2
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2024
    In:  Frontiers in Marine Science Vol. 11 ( 2024-6-18)
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 11 ( 2024-6-18)
    Abstract: The blackchin guitarfish Glaucostegus cemiculus has suffered severe declines and regional extirpation throughout its known distributions. While this species and its relative, the common guitarfish Rhinobatos rhinobatos , have been described in the Mediterranean Sea with co-occurring habitat ranges, no research has recorded the existence or extent of these two separate populations along the Israeli coastal waters. Along a particular coast in Israel, Ma’agan Michael, fishermen have reported annual observations of juvenile guitarfish between June to November for the last forty years. Based on these citizen-based observations the main research objective is to establish whether Ma’agan Michael fulfils all three criteria from the literature by Dr Michelle Heupel, allowing it to be acknowledged as a nursery ground for G. cemiculus . The methodology built for this objective integrates biological characteristics data with the identification of a recurrent seasonal distribution. Visual surveys exhibited a significantly higher abundance in Ma’agan Michael when compared to an adjacent area (Caesarea), with 2,096 recorded observations overall. Additionally, using a species-specific modified Catch and Release protocol, a total of 492 juveniles were captured with a beach seine net. During these capturing events, individuals were morphometrically measured and sampled for future genetic analyses. Out of these, 327 specimens were also fitted for PIT tags to track recaptures in subsequent captures. The highest abundance of neonates was caught from August to September each year (2017–2019), and all individuals captured during this study were identified in the field as G. cemiculus , ranging from 20–35 cm in length (85% of captures). Many specimens had an umbilical cord scar (n = 88), with a large percentage possessing visual remains of the yolk sac. For the first time, this study provides an inter-year description of the species Glaucostegus cemiculus present along the Israeli shoreline.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2757748-X
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-2-4)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-2-4)
    Abstract: Hyper IgE syndromes (HIES) are a group of rare primary immunodeficiency characterized by high levels of serum IgE, cold abscesses, pulmonary infections, and eczema. ZNF341 deficiency was described in 2018 in 11 patients clinically diagnosed previously with HIES. Eight of those patients, all offspring of consanguineous couples, are from three families who live in a Muslim village in Israel which has approximately 15,000 residents. Objective Our study aimed to evaluate the prevalence of ZNF341 mutation in the population of the village. Methods Three hundred DNA samples of females were included in the study. The samples belong to females that were referred to the Meir Medical Center for prenatal genetic testing before pregnancy, during 2017-2019: 200 samples were from the village, and 100 samples of Muslim females were from other villages. All samples were tested by Sanger sequencing for the ZNF341 mutation (c.904C & gt;T, NM_001282933.1). Results Heterozygous nonsense mutation in ZNF341 was found in ten samples (5%) of the study group compared to zero in the control group (p & lt;0.01). Conclusion The carrier frequency of the mutation in ZNF341 in the studied village population is 1:20. This high frequency is probably due to founder mutation and consanguineous marriages.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 6
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 11 ( 2021-1-21)
    Abstract: Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. Aim: To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. Methods: MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Results: Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1–66 years, with increased prevalence in children (19% compared to 6.7% in adults) ( p & lt; 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31–40 years (16.6%). Conclusions: MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564214-5
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  • 7
    In: Transplant International, Frontiers Media SA, Vol. 36 ( 2023-3-9)
    Abstract: Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p & lt; 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p & lt; 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.
    Type of Medium: Online Resource
    ISSN: 1432-2277
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 1463183-0
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  • 8
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-8-9)
    Abstract: Recent advances in the field of cell therapy have proposed new solutions for tissue repair and regeneration using various cell delivery approaches. Here we studied ex vivo a novel topical delivery system of encapsulated cells in hybrid polyethylene glycol-fibrinogen (PEG-Fb) hydrogel microspheres to respiratory tract models. We investigated basic parameters of cell encapsulation, delivery and release in conditions of inflamed and damaged lungs of bacterial-infected mice. The establishment of each step in the study was essential for the proof of concept. We demonstrated co-encapsulation of alveolar macrophages and epithelial cells that were highly viable and equally distributed inside the microspheres. We found that encapsulated macrophages exposed to bacterial endotoxin lipopolysaccharide preserved high viability and secreted moderate levels of TNFα, whereas non-encapsulated cells exhibited a burst TNFα secretion and reduced viability. LPS-exposed encapsulated macrophages exhibited elongated morphology and out-migration capability from microspheres. Microsphere degradation and cell release in inflamed lung environment was studied ex vivo by the incubation of encapsulated macrophages with lung extracts derived from intranasally infected mice with Yersinia pestis , demonstrating the potential in cell targeting and release in inflamed lungs. Finally, we demonstrated microsphere delivery to a multi-component airways-on-chip platform that mimic human nasal, bronchial and alveolar airways in serially connected compartments. This study demonstrates the feasibility in using hydrogel microspheres as an effective method for topical cell delivery to the lungs in the context of pulmonary damage and the need for tissue repair.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2013
    In:  Frontiers in Human Neuroscience Vol. 7 ( 2013)
    In: Frontiers in Human Neuroscience, Frontiers Media SA, Vol. 7 ( 2013)
    Type of Medium: Online Resource
    ISSN: 1662-5161
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2013
    detail.hit.zdb_id: 2425477-0
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-8-3)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-8-3)
    Abstract: CD45, the predominant transmembrane tyrosine phosphatase in leukocytes, is required for the efficient induction of T cell receptor signaling and activation. We recently reported that the CD45-intracellular signals in peripheral blood mononuclear cells (PBMCs) of triple negative breast cancer (TNBC) patients are inhibited. We also reported that C24D, an immune modulating therapeutic peptide, binds to CD45 on immune-suppressed cells and resets the functionality of the immune system via the CD45 signaling pathway. Various studies have demonstrated that also viruses can interfere with the functions of CD45 and that patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are immune-suppressed. Given the similarity between the role of CD45 in viral immune suppression and our findings on TNBC, we hypothesized that the C24D peptide may have a similar “immune-resetting” effect on PBMCs from COVID-19 patients as it did on PBMCs from TNBC patients. We tested this hypothesis by comparing the CD45/TCR intracellular signaling in PBMCs from ten COVID-19 patients vs. PBMCs from ten healthy volunteers. Herein, we report our findings, demonstrating the immune reactivating effect of C24D via the phosphorylation of the tyrosine 505 and 394 in Lck, the tyrosine 493 in ZAP-70 and the tyrosine 172 in VAV-1 proteins in the CD45 signaling pathway. Despite the relatively small number of patients in this report, the results demonstrate that C24D rescued CD45 signaling. Given the central role played by CD45 in the immune system, we suggest CD45 as a potential therapeutic target.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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