Objective: Relapsed and refractory CD19-positive B-cell acute
lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)
are the focus of studies on hematological cancers. Treatment of
these ...malignancies has undergone recent transformation with the
development of new gene therapy and molecular biology techniques,
which are safer and well-tolerated therapeutic approaches. The CD19
antigen is the most studied therapeutic target in these hematological
cancers. This study reports the results of clinical-grade production,
quality control, and in vivo efficacy processes of ISIKOK-19 cells as the
first academic clinical trial of CAR-T cells targeting CD19-expressing B
cells in relapsed/refractory ALL and NHL patients in Turkey.
Materials and Methods: We used a lentiviral vector encoding the
CD19 antigen-specific antibody head (FMC63) conjugated with the
CD8-CD28-CD3ζ sequence as a chimeric antigen receptor (CAR) along
with a truncated form of EGFR (EGFRt) on human T-lymphocytes
(CAR-T). We preclinically assessed the efficacy and safety of the
manufactured CAR-T cells, namely ISIKOK-19, from both healthy
donors’ and ALL/NHL patients’ peripheral blood mononuclear cells.
Results: We showed significant enhancement of CAR lentivirus
transduction efficacy in T-cells using BX-795, an inhibitor of the
signaling molecule TBK1/IKKƐ, in order to cut the cost of CAR-T cell
production. In addition, ISIKOK-19 cells demonstrated a significantly
high level of cytotoxicity specifically against a CD19+ B-lymphocyte
cancer model, RAJI cells, in NOD/SCID mice.
Conclusion: This is the first report of preclinical assessment of
efficacy and safety analysis of CAR-T cells (ISIKOK-19) targeting
CD19-expressing B cells in relapsed/refractory ALL and NHL patients
in Turkey.
This study investigates the importance of the determinants affecting the adoption and usage of blockchain-based SCM systems in the context of organizations. Hence, an SLR method was followed to ...uncover critical determinants in the literature. Then, a research model, including 14 key determinants, was developed based on the TOE Framework. Subsequently, the AHP method was applied to rank the adoption determinants. The findings reveal that environment-related determinants are more critical than technology-related or organization-related determinants.
Accumulation of Gamma aluminium oxide nanoparticles γ-Al
2
O
3
NPs significant impact on aquatic ecosystems. However, the toxicity of γ-Al
2
O
3
NPs in aquatic organisms has been limited ...investigated. This study investigated histopathological changes and antioxidant responses induced by different concentrations of γ-Al
2
O
3
NPs in Mytilus galloprovincialis.
In this study, mussels were exposed to different concentrations of 5 nm γ-Al
2
O
3
NPs (0, 5, 20 and 40 mg/L) for 96 h under controlled laboratory conditions. Gill and digestive gland from mussels were assessed to histopathological (light microscopy, histopathological condition indices, digestive gland tubule types), SOD, CAT, GPx activities.
Histopathological indices calculated higher, and significantly different in all exposure groups compared to the control group in gill and digestive gland (p < 0.05). Atrophic phase tubules proportion very high in 20 and 40 mg/L γ-Al
2
O
3
NPs exposure groups. No significant changes in CAT activities in the gill and digestive gland (p > 0.05). Superoxide dismutase (SOD) activities significantly different (p ≤ 0.05) in the digestive gland from 20 mg/L γ-Al
2
O
3
NPs exposures, and GPx activities significantly different (p < 0.05) in gill from 40 mg/L γ-Al
2
O
3
NPs exposures.
These results indicate that contamination of γ-Al
2
O
3
NPs negatively affects the aquatic organism.
Anomaly detection in spatiotemporal data is a challenging problem encountered in a variety of applications including urban traffic monitoring. Existing anomaly detection methods mostly focus on point ...anomalies and cannot deal with temporal and spatial dependencies that arise in spatiotemporal data. Tensor-based anomaly detection methods have been proposed to address this problem. While these methods are able to capture the dependencies across the different modes, they are mostly supervised and do not take the particular nature of anomalies into account. In this paper, we introduce an unsupervised tensor-based anomaly detection method that simultaneously considers the sparse and spatiotemporally smooth nature of anomalies. The anomaly detection problem is formulated as a regularized robust low-rank + sparse tensor decomposition where the spatiotemporal smoothness of the anomalies is quantified by the graph total variation with respect to the underlying spatial and temporal graphs. This minimization ensures that the extracted anomalies are temporally persistent and spatially smooth. The proposed framework is evaluated on both synthetic and real spatiotemporal urban traffic data.
In this study, alpha and gamma iron oxide nanoparticles, characterizations, toxic effects after being exposed to rainbow trout (
Oncorhynchus mykiss
) at 0, 1, 10 and 25 mg/L concentrations for 10 ...days, and then 10-day recovery period without any nanoparticle exposure were examined for histopathological (kidney, liver and gill), hematological, iron accumulation and potential for oxidative stress (TBARS and GSH). Histopathological damages significant at the exposure of increasing concentrations of both nanoparticles (increase in melanomacrophage aggregations, epithelial tissue deformations, cytoplasmic vacuolizations, fatty changes, necrosis, pyknosis, hyperplasia, hypertrophy, lamellar fusions, capillary dilatations). Gamma nanoparticles were determined to accumulate more than the alpha nanoparticles. The most Fe accumulation was detected in the liver. The findings of oxidative stress parameters showed that both nanoparticles have the potential to generate oxidative stress. It was concluded that the exposure of alpha and gamma nanoparticles at specified concentrations and durations had a toxic effect on rainbow trout and the toxicity of these nanoparticles was similar.
Pinna nobilis (fan mussel) is one of the most important endemic bivalve molluscs in the Mediterranean and mass mortality events were observed in these mussels in recent years. In this study, we ...report mass mortalities caused by Haplosporidium pinnae, which has been spreading in the Mediterranean for 3 years, and reached the Çanakkale Strait, which is the entrance of the Marmara and the Black Sea.
Field observations during sampling and subsequent histopathological, biochemical, genetic, and microbiological analyses were carried out.
These analyses showed that H. pinnae infection spread among the natural beds of P. nobilis, causing severe tissue damage and oxidative stress. Our phylogenetic analyses suggested that the parasite spread through the Mediterranean much faster than thought. The results showed that vibriosis originating from Vibrio coralliilyticus, Vibrio tubiashii, Vibrio mediterranei, and Vibrio hispanicus, acted together with H. pinnae in infected individuals and caused death.
It is highly probable that the spread of H. pinnae to the Sea of Marmara and the Black Sea may occur earlier than expected, and it was concluded that mass deaths were caused by co-infection with H. pinnae and a geographically specific marine pathogen that can infect P. nobilis populations.
The extensive utilization of boric acid, particularly in industrial and agricultural sectors, also engenders concerns regarding the toxicity of boron and its derivatives. Particularly, the behavior ...of boric acid at increasing concentrations in aquatic ecosystems remains poorly understood. In light of these concerns, this study aimed to investigate the toxicity of boric acid in bivalves, which occupy a critical position in the food chain. Specimens of Ruditapes decussatus, which had not been previously exposed to any pollutants and were cultivated under controlled conditions, were subjected to three different concentrations of boric acid (0.05 mg/L, 0.5 mg/L, and 5 mg/L) in vitro for 96 h. Following the exposure period, the specimens were assessed for histological changes (the mantle, gill, and digestive gland) and specific oxidative parameters (the gill and digestive gland), including superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase, and lipid peroxidation (LPO). The research findings indicated that boric acid primarily induced oxidative damage at the applied concentrations and increased antioxidant levels (p < 0.05). Moreover, although no significant histopathological abnormalities were observed in the examined histological sections, subtle changes were noted. This study evaluated the potential adverse effects of boric acid on bivalves, which are crucial components of the aquatic food chain, utilizing histological and specific physiological parameters following its introduction into aquatic environments. It is anticipated that the findings of this study will contribute to the development of new insights and perspectives regarding the extensive use of boric acid.
The observation of mortality in Mediterranean mussels (Mytilus galloprovincialis) distributed in the Çanakkale Strait in recent years was influential in developing the research question for this ...study. In this study, the presence of bacteria (Vibrio spp.) and parasites (Marteilia spp. and Haplosporidium spp.) in mussels collected from Kumkale, Kepez, and Umurbey stations in the Çanakkale Strait was investigated seasonally. Microbiological findings, histopathology, oxidative stress enzymes and their gene expressions, lipid peroxidation, lysosomal membrane stability, and changes in haemolymph were examined. In summer samples, both the defence system and the extent of damage were higher in gill tissue. In winter samples, enzyme activities and lipid peroxidation were found to be predominantly higher in digestive gland tissues. Histological examinations and Hemacolor staining revealed the presence of protozoan cysts, and for bacterial examination, molecular analysis performed after culturing revealed the presence of 7 Vibrio species. While the total numbers of heterotrophic bacteria detected in all samples were at acceptable levels, the predominance of Vibrio spp. numbers among the total heterotrophic bacteria detected in almost all samples were noteworthy. The total hemocyte count was calculated as 5.810(4)±0.58 (cells/mm3) in winter and 7.210(4)±1.03 (cells/mm3) in summer. These factors are considered to be possible causes of mussel mortality.
•The health status of Mediterranean mussel samples distributed in the Çanakkale Strait was evaluated from different perspectives.•Mussels' various tissue histology and associated oxidative parameters were assessed alongside gene expressions of enzyme levels, serving as indicators for oxidative stress detection.•The microbiological flora of samples were revealed and examined at the molecular level.•The observations imply that the decline in mussel populations subsequent to mucilage events may be attributed to potential parasitic influences.
This investigation aims to assess the influence of a mobile application and smart devices on cardiopulmonary exercise testing (CPET) over a one-year period in individuals who have high risk for ...cardiovascular disease.
This is a post-hoc subgroup analysis of Lifestyle Intervention Using Mobile Technology in Patients with High Cardiovascular Risk: A Pragmatic Randomised Clinical Trial (LIGHT). In the intervention plus standard care standard standard care arms, 138 and 103 patients were recruited, respectively. The 1-year VO
2
measurements were adjusted to the baseline VO
2
measurements as the study's endpoint. VO
2
measurements were taken for each subject during the randomisation and final CPET examinations.
The intervention plus standard care improved VO
2
measurements by 1.1 (adjusted treatment effect 1.1, 95% confidence interval (CI): 0.8, 1.4, p < 0.001) compared to standard care following 1-year follow-up.
At a 1-year follow-up, the smart device and mobile application technologies increased VO
2
measurements in individuals with high cardiovascular risk compared to conventional treatment alone.
This investigation aims to evaluate the effect of a mobile application and smart devices on frequency and time domains of heart rate variability (HRV) in diabetic patients in 1-year follow-up.
This ...is post-hoc analysis of a diabetic subgroup of "Lifestyle Intervention usinG mobile technology in patients with high cardiovascular risk: a pragmatic randomized clinical Trial" (LIGHT). One hundred and nine and 118 patients were enrolled in two arms: the intervention plus usual care and the usual care arm. The study outcome was the 1-year HRV parameters adjusted to the baseline HRV parameters. HRV measures were recorded for every patient at the randomization and final visits with 24-hour Holter monitoring.
There was an improvement in the standard deviation of normal to normal (SDNN) R-R intervals 24-hour by 4.8 (adjusted treatment effect 4.8, 95% confidence interval CI, 0.1-9.5; P = 0.044) in the intervention-plus-usual-care arm compared to usual care after a 1-year follow-up. The improvement was also experienced in other HRV time domains including standard deviation of the mean R-R intervals calculated over a 5-minute period, SDNN, square root of the mean squared difference of successive R-R intervals, and the percentage of the differences between adjacent normal R-R intervals exceeding 50 milliseconds. A significant enhancement was also detected in HRV frequency domains of total power low frequency and high frequency in the intervention plus usual care compared to usual care after a 1-year follow-up.
The mobile application and smart device technology compared to usual care alone improved HRV parameters in diabetic patients at 1-year follow-up.
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