Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both and models.

Unlabelled: Recombinant chimeric horsepox virus (TNX-801) is a preclinical vaccine in development against mpox and smallpox. In this report, we investigated the potential phenotypic differences in and models between TNX-801 and older vaccinia virus (VACV)-based vaccine strains (VACV-Lis and VACV-NYCBH) used in the eradication of smallpox as well as VACV-WR, VACV-IHD, and MVA. TNX-801 displayed a small plaque phenotype (~1-2 mm) in BSC-40 and Vero-E6 cells.

Preemptive Approach to Plerixafor Use Is Optimal in Patients With Relapsed/Refractory Germ Cell Tumors Undergoing Peripheral Blood Hematopoietic Stem Cell Collection: Effect on Collection Days, Yields, and Cost.

Evidence describing the use of plerixafor in the off-label population of relapsed/refractory germ cell tumors (GCT) is limited. We aim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022.

Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates.

TNX-1800 is a synthetically derived live recombinant chimeric horsepox virus (rcHPXV) vaccine candidate expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated with no serious adverse events or significant changes in clinical parameters.

Immunogenicity and Tolerability of a SARS-CoV-2 TNX-1800, a Live Recombinant Poxvirus Vaccine Candidate, in Syrian Hamsters and New Zealand White Rabbits.

TNX-1800 is a preclinical stage synthetic-derived live attenuated chimeric horsepox virus vaccine engineered to express the SARS-CoV-2 spike (S) gene. The objectives of this study were to assess the safety, tolerability, and immunogenicity of TNX-1800 administration in Syrian golden hamsters and New Zealand white rabbits. Animals were vaccinated at three doses via percutaneous inoculation.

Primed for change: The effect of a blood prime on peripheral blood stem cell collection and accuracy of a prediction tool in pediatric patients.

Pediatric apheresis collection of peripheral blood stem cells for autologous transplantation often requires use of a blood prime. We evaluated the relationship between pre-apheresis blood CD34 counts and final CD34 yield with use of a blood prime. Forty patients underwent apheresis stem cell collection in a 5 year period in our hospital, of which 27 required blood priming of the apheresis machine.

Development of a rapid image-based high-content imaging screening assay to evaluate therapeutic antibodies against the monkeypox virus.

Antibody-based therapy is emerging as a critical therapeutic countermeasure to treat acute viral infections by offering rapid protection against clinical disease. The advancements in structural biology made it feasible to rationalize monoclonal antibodies (mAbs) by identifying key and, possibly, neutralizing epitopes of viral proteins for therapeutic purposes. A critical component in assessing mAbs during pandemics requires the development of rapid but detailed methods to detect and quantitate the neutralization activity.

Characterization and Function of Cryopreserved Bone Marrow from Deceased Organ Donors: A Potential Viable Alternative Graft Source.

Despite the readily available graft sources for allogeneic hematopoietic cell transplantation (alloHCT), a significant unmet need remains in the timely provision of suitable unrelated donor grafts. This shortage is related to the rarity of certain HLA alleles in the donor pool, nonclearance of donors owing to infectious disease or general health status, and prolonged graft procurement and processing times. An alternative hematopoietic progenitor cell (HPC) graft source obtained from the vertebral bodies (VBs) of deceased organ donors could alleviate many of the obstacles associated with using grafts from healthy living donors or umbilical cord blood (UCB).

Outcomes of pediatric patients with therapy-related myeloid neoplasms.

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival.

How old is too old? engraftment of human peripheral blood stem cells cryopreserved for up to 18 years - implications for clinical transplantation and stability programs.

Background: Peripheral blood stem cells (PBSC) are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant. Long term cryopreservation is commonly defined as five years or longer, and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft. Clinical programs, stem cell banks, and regulatory and accrediting agencies interested in product stability would benefit from such data.

SARS-CoV-2 Shedding from Asymptomatic Patients: Contribution of Potential Extrapulmonary Tissue Reservoirs.

The ongoing pandemic COVID-19, caused by SARS-CoV-2, has already resulted in more than 3 million cases and more than 200,000 deaths globally. Significant clinical presentations of COVID-19 include respiratory symptoms and pneumonia. In a minority of patients, extrapulmonary organs (central nervous system, eyes, heart, and gut) are affected, with detection of viral RNA in bodily secretions (stool, tears, and saliva).

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque's and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines.

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge.

Low CD34 Cell Doses Are Associated with Increased Cost and Worse Outcome after Tandem Autologous Stem Cell Transplantation in Patients with Relapsed or Refractory Germ Cell Tumors.

Tandem autologous stem cell transplantation (ASCT) improves long-term survival of platinum-refractory germ cell tumors (GCT) patients. Studies, predominantly in lymphoma, showed that CD34 cell doses > 5.0 × 10/kg/single transplant led to decreased resource utilization.

Synergistic antiviral activity of Sofosbuvir and type-I interferons (α and β) against Zika virus.

Zika virus (ZIKV) is transmitted by mosquitoes and causes Dengue-like illness, neurological symptoms such as Guillain-Barré Syndrome and microcephaly in children born to infected pregnant mothers. Recently, the World Health Organization (WHO) declared ZIKV infection as a Global Health Emergency. However, there are no known prophylactic or therapeutic measures against this virus.

Development of a Zika Virus Infection Model in Cynomolgus Macaques.

Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates.

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus.

Despite the rapid spread of Zika virus (ZIKV) infection and associated neurological complications in the America's, prophylactic or therapeutic countermeasures are not currently available. This is mostly due to the fact that until recently there was no presumed need for medical intervention since there was no association between ZIKV infection and significant human morbidity. Consequently, there are currently no tools due mostly to the lack of sensitive cell based assays amenable for identification of ZIKV inhibitors.

Fabrication of Poly-l-lactic Acid/Dicalcium Phosphate Dihydrate Composite Scaffolds with High Mechanical Strength-Implications for Bone Tissue Engineering.

Scaffolds were fabricated from poly-l-lactic acid (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting. Sodium citrate and PLLA were used to improve the mechanical properties of the DCPD scaffolds. The resulting PLLA/DCPD composite scaffold had increased diametral tensile strength and fracture energy when compared to DCPD only scaffolds (1.

FANCA safeguards interphase and mitosis during hematopoiesis in vivo.

The Fanconi anemia (FA/BRCA) signaling network controls multiple genome-housekeeping checkpoints, from interphase DNA repair to mitosis. The in vivo role of abnormal cell division in FA remains unknown. Here, we quantified the origins of genomic instability in FA patients and mice in vivo and ex vivo.

The effect of diluted triple and double antibiotic pastes on dental pulp stem cells and established Enterococcus faecalis biofilm.

Objectives: To investigate the effect of various dilutions of antibiotic medicaments used in endodontic regeneration on the survival of human dental pulp stem cells (DPSCs) and to determine their antibacterial effect against established Enterococcus faecalis biofilm.

Materials And Methods: The cytotoxic and antibacterial effects of different triple (TAP) and double antibiotic paste (DAP) dilutions (0.125, 0.

Temozolomide-mediated DNA methylation in human myeloid precursor cells: differential involvement of intrinsic and extrinsic apoptotic pathways.

Purpose: An understanding of how hematopoietic cells respond to therapy that causes myelosuppression will help develop approaches to prevent this potentially life-threatening toxicity. The goal of this study was to determine how human myeloid precursor cells respond to temozolomide (TMZ)-induced DNA damage.

Experimental Design: We developed an ex vivo primary human myeloid precursor cells model system to investigate the involvement of cell-death pathways using a known myelosuppressive regimen of O(6)-benzylguanine (6BG) and TMZ.

Effects of DCPD cement chemistry on degradation properties and cytocompatibility: comparison of MCPM/β-TCP and MCPM/HA formulations.

Dicalcium phosphate dihydrate (DCPD) cements are attractive biomaterials for bone repair, and a number of different DCPD cement formulations have been proposed in the literature. In this study, we have specifically compared monocalcium phosphate monohydrate (MCPM)/hydroxyapatite (HA) and MCPM/β-tricalcium phosphate (β-TCP) formulations to test the hypothesis that DCPD cement chemistry affects the degradation properties and cytocompatibility of the cement. Using simple in vitro models we found that MCPM/β-TCP formulations degraded primarily by DCPD dissolution, which was associated with a slight pH drop and relatively low mass loss.

Manufacturing and banking of mesenchymal stem cells.

Introduction: Mesenchymal stem cells (MSC) and MSC-like cells hold great promise and offer many advantages for developing effective cellular therapeutics. Current trends indicate that the clinical application of MSC will continue to increase markedly. For clinical applications, large numbers of MSC are usually required, ideally in an off-the-shelf format, thus requiring extensive MSC expansion ex vivo and subsequent cryopreservation and banking.

Poly(propylene fumarate) reinforced dicalcium phosphate dihydrate cement composites for bone tissue engineering.

Calcium phosphate cements have many desirable properties for bone tissue engineering, including osteoconductivity, resorbability, and amenability to rapid prototyping-based methods for scaffold fabrication. In this study, we show that dicalcium phosphate dihydrate (DCPD) cements, which are highly resorbable but also inherently weak and brittle, can be reinforced with poly(propylene fumarate) (PPF) to produce strong composites with mechanical properties suitable for bone tissue engineering. Characterization of DCPD-PPF composites revealed significant improvements in mechanical properties for cements with a 1.

In vitro degradation and cytocompatibility of dicalcium phosphate dihydrate cements prepared using the monocalcium phosphate monohydrate/hydroxyapatite system reveals rapid conversion to HA as a key mechanism.

We previously showed that dicalcium phosphate dihydrate (DCPD) cements can be prepared using monocalcium phosphate monohydrate (MCPM) and hydroxyapatite (HA). In this study, we have characterized the degradation properties and biocompatibility of these novel cements. To study the degradation properties, cements were prepared using MCPM:HA molar ratios of 4:1, 2:1, 2:3, and 2:5.

Lung function before and after pediatric allogeneic hematopoietic stem cell transplantation: a predictive role for DLCOa/VA.

Background: Pre-allogeneic hematopoietic stem cell transplantation (aHSCT) and post-aHSCT lung function of 41 eligible patients at Riley Hospital for Children were assessed to identify risk factors for post-aHSCT morbidity and mortality.

Observations: One year post-aHSCT pulmonary function tests were significantly lower compared with baseline. These findings recovered at 2 years post-aHSCT.