Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing Oximetry Response to Chimeric Antigen Receptor T-cell Therapy against Glioma with 19F MRI in a Murine Model.

Purpose To assess the cell-specific, intracellular partial pressure of oxygen (Po2) dynamics of both tumor and chimeric antigen receptor (CAR) T cells in a murine immunotherapy model. Materials and Methods Human glioblastoma cells or human T cells were intracellularly labeled with perfluorocarbon nanoemulsion droplet sensors prior to in vivo injection in severe combined immunodeficient mice to measure Po2 in the two cell types in response to treatment. Two main sets of experiments were performed: (a) mice were injected in the flank with perfluorocarbon-labeled human glioblastoma cells and were then inoculated with either CAR T cells or untransduced T cells or were untreated 5 days after tumor inoculation; and (b) mice with unlabeled glioblastoma tumors were inoculated with perfluorocarbon-labeled CAR T cells or untransduced T cells 5 days after tumor inoculation. Longitudinal fluorine 19 (19F) spin-lattice relaxation time measurements of the tumor mass were used to ascertain absolute Po2 in vivo. Results were analyzed for significance using an analysis of variance, a linear mixed-effect model, and a Pearson correlation coefficient test, as appropriate. Results The intracellular tumor cell Po2 temporal dynamics exhibited delayed, transient hyperoxia at 3 days after infusion of CAR T cells, commensurate with significant tumor cell killing and CAR T-cell infiltration, as observed by bioluminescence imaging and histologic findings. Conversely, no significant changes were detected in CAR or untransduced T-cell intracellular Po2 over time in tumor using these same methods. Moreover, it was observed that the total 19F tumor cell signal quenches with treatment, consistent with rapid tissue clearance of probe from apoptotic tumor cells. Conclusion Cell-specific Po2 measurements using perfluorocarbon probes can provide insights into effector cell function and tumor response in cellular immunotherapeutic cancer models.Keywords: Animal Studies, MR-Imaging, MR-Spectroscopy, Molecular Imaging-Cancer, Molecular Imaging-Immunotherapy Supplemental material is available for this article. © RSNA, 2021See also commentary by Bulte in this issue.
ALK2 Receptor Kinase Association with FKBP12.6 Is Structurally Conserved with the ALK2-FKBP12 Complex

The immunophilin FKBP12 is a known inhibitor of type I BMP and TGF-β receptors that competes for binding with their substrate SMADs. FKBP12 and the close paralog FKBP12.6 additionally assemble with ryanodine receptors to control Ca2+ release. Binding of FKBP12.6 to BMP/TGF-β receptors has yet to be investigated, but appears plausible given its high sequence similarity to FKBP12. Here, we found that FKBP12.6 can assemble with BMP and TGF-β-family type I receptors, but not with type II receptors. Cellular immunoprecipitation confirmed similar binding of FKBP12 and FKBP12.6 to the BMP receptor ALK2 (ACVR1), a known target of mutations in the congenital syndrome fibrodysplasia ossificans progressiva (FOP), as well as the pediatric brain tumor diffuse intrinsic pontine glioma (DIPG). SEC-MALS analyses using purified proteins indicated a direct 1:1 interaction between FKBP12.6 and the receptor’s cytoplasmic domains. The 2.17 Å structure of this ALK2-FKBP12.6 complex bound to the inhibitor dorsomorphin showed FKBP12.6 binding to the GS domain of ALK2 in a manner equivalent to the FKBP12 complex, with ALK2 residues Phe198 and Leu199 extending into the FK506-binding pocket of FKBP12.6. These findings suggest a level of redundancy in FKBP-family regulation of BMP and TGF-β signaling.
Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.
Adverse Childhood Experiences and Psychological Well-Being in Chinese College Students: Mediation Effect of Mindfulness

Literature on the antecedents of psychological well-being (PWB) has found that adverse childhood experiences (ACEs) and mindfulness are associated with PWB; less is known, however, about the role of mindfulness, a type of emotional and self-regulation, in the pathway between ACEs and PWB. This study used data from 1871 college students across China to examine the relation between ACEs and PWB, and whether the relation was mediated by mindfulness. The findings from structural equation modelling indicate a statistically significant negative association between ACEs and PWB, while mindfulness was strongly and positively associated with PWB. The effect of ACEs on PWB was reduced once mindfulness was controlled for in the analysis. This provides evidence that mindfulness was able to partially mediate the effects of negative life experiences on psychological well-being. This calls for mindfulness interventions targeted toward students with a history of ACEs to buffer the effects of ACEs on PWB.
Evaluation of Kisspeptin levels in prepubertal obese and overweight children: sexual dimorphism and modulation of antioxidant levels.

OBJECTIVE Kisspeptin, neuropeptide involved in puberty beginning and regulation of pituitary-gonadal axis, has been shown to stimulate antioxidant defenses in murine models. Its levels are greater in females than males and also in obese prepubertal girls. Therefore, our aim was to evaluate sex-related differences in prepubertal obese patients and the relationships of Kisspeptin with metabolic/hormonal parameters. PATIENTS AND METHODS We studied Kisspeptin concentrations in 54 children (22 males and 32 females, Tanner stage 1), 5-12 ys, classified according to Cole's criteria into 17 overweight and 37 obese; 25 normal-weight children, aged 6-12 years, were studied as controls. We evaluated metabolic (glucose and insulin levels after oral glucose load, total- LDL- HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters. Moreover, total antioxidant capacity (TAC) was evaluated by spectrophotometric method, using the system H202-metmyoglobin-ABTS. Kisspeptin levels were measured by RIA. RESULTS We did not find significant differences between obese and normal-weight children, but obese males presented significantly lower levels than females. Kisspeptin did not correlate with BMI, HOMA-IR, Insulin peak levels and TAC; a significant correlation was found between Kisspeptin and fT3 (r2=0.25; p=0.003) in the obese group; leptin levels, significantly greater in obese vs. overweight and control children, significantly correlated with TAC (r2=0.39; p=0.03). CONCLUSIONS These data suggest that both hormones could modulate antioxidants, Kisspeptin indirectly via influence on thyroid hormones, and Leptin by a direct effect. This mechanism seems to be sex-related, not attributable to peripheral steroid levels. Further studies can clarify the complex interrelationship between central and peripheral Kisspeptin secretion and oxidative stress in children obesity.
Electrical Properties of Cerium‐Doped BaTiO3

The high-temperature equilibrium electrical conductivity of Ce-doped BaTiO3 was studied in terms of oxygen partial pressure, P(O2), and composition. In (Ba1−xCex)TiO3, the conductivity follows the −1/4 power dependence of P(O2) at high oxygen activities, which supports the view that metal vacancies are created for the compensation of Ce donors, and is nearly independent of P(O2) where electron compensation prevails at low P(O2). When Ce is substituted for the normal Ti sites, there is no significant change in conductivity behavior compared with undoped BaTiO3, indicating the substitution of Ce as Ce4+ for Ti4+ in Ba(Ti1−yCey)O3. The Curie temperature (Tc) was systematically lowered when Ce3+ was incorporated into Ba2+ sites, whereas the substitution of Ce4+ for Ti4+ sites resulted in no change in this parameter.
Lentiviral Vector Bioprocessing

Lentiviral vectors (LVs) are potent tools for the delivery of genes of interest into mammalian cells and are now commonly utilised within the growing field of cell and gene therapy for the treatment of monogenic diseases and adoptive therapies such as chimeric antigen T-cell (CAR-T) therapy. This is a comprehensive review of the individual bioprocess operations employed in LV production. We highlight the role of envelope proteins in vector design as well as their impact on the bioprocessing of lentiviral vectors. An overview of the current state of these operations provides opportunities for bioprocess discovery and improvement with emphasis on the considerations for optimal and scalable processing of LV during development and clinical production. Upstream culture for LV generation is described with comparisons on the different transfection methods and various bioreactors for suspension and adherent producer cell cultivation. The purification of LV is examined, evaluating different sequences of downstream process operations for both small- and large-scale production requirements. For scalable operations, a key focus is the development in chromatographic purification in addition to an in-depth examination of the application of tangential flow filtration. A summary of vector quantification and characterisation assays is also presented. Finally, the assessment of the whole bioprocess for LV production is discussed to benefit from the broader understanding of potential interactions of the different process options. This review is aimed to assist in the achievement of high quality, high concentration lentiviral vectors from robust and scalable processes.
Genomic Architecture of Phenotypic Plasticity in Response to Water Stress in Tetraploid Wheat

Phenotypic plasticity is one of the main mechanisms of adaptation to abiotic stresses via changes in critical developmental stages. Altering flowering phenology is a key evolutionary strategy of plant adaptation to abiotic stresses, to achieve the maximum possible reproduction. The current study is the first to apply the linear regression residuals as drought plasticity scores while considering the variation in flowering phenology and traits under non-stress conditions. We characterized the genomic architecture of 17 complex traits and their drought plasticity scores for quantitative trait loci (QTL) mapping, using a mapping population derived from a cross between durum wheat (Triticum turgidum ssp. durum) and wild emmer wheat (T. turgidum ssp. dicoccoides). We identified 79 QTLs affected observed traits and their plasticity scores, of which 33 reflected plasticity in response to water stress and exhibited epistatic interactions and/or pleiotropy between the observed and plasticity traits. Vrn-B3 (TaTF1) residing within an interval of a major drought-escape QTL was proposed as a candidate gene. The favorable alleles for most of the plasticity QTLs were contributed by wild emmer wheat, demonstrating its high potential for wheat improvement. Our study presents a new approach for the quantification of plant adaptation to various stresses and provides new insights into the genetic basis of wheat complex traits under water-deficit stress.
Effect of Excessive Body Weight and Emotional Disorders on the Course of Pregnancy and Well-Being of a Newborn before and during COVID-19 Pandemic

This study aimed to evaluate whether excessive body weight and the COVID-19 pandemic affect depression, and subsequently whether depression, excessive body weight, and the COVID-19 pandemic affect the course of pregnancy, as well as the well-being of a newborn. The research material included data retrieved from the medical records of 280 pregnant women who were provided with care by medical facilities in Lublin (100 women with normal weight, 100 overweight women, 50 with Class I and 30 with Class II obesity). They completed a Beck depression inventory (BDI) in pregnancy twice, in order to assess the risk of occurrence of postpartum depression. Pre-pregnancy BMI positively correlated with the severity of depression, both at 10–13 weeks of pregnancy (p < 0.001), and at 32 weeks of pregnancy (p < 0.001). The higher the pre-pregnancy BMI, on average the higher the severity of depression. The severity of depression was significantly higher during the pandemic than before it in women with normal body weight before pregnancy (p < 0.001), as well as in those overweight (p < 0.001) and with Class II obesity (p = 0.015). Excessive body weight before pregnancy leads to depressive disorders during pregnancy, increases the risk of preterm delivery, and exerts a negative effect on the state of a newborn. Depressive symptoms among pregnant, overweight and obese women intensified during the COVID-19 pandemic.
Fast Stent Retrieval during Mechanical Thrombectomy Improves Recanalization in Patients with the Negative Susceptibility Vessel Sign

A fast stent retrieval during mechanical thrombectomy is safe and improves the retrieval of clots with the negative susceptibility vessel sign. BACKGROUND AND PURPOSE: In acute ischemic stroke, the negative susceptibility vessel sign on T2*-weighted images traditionally highlights fibrin-rich clots, which are particularly challenging to remove. In vitro, fast stent retrieval improves fibrin-rich clot extraction. We aimed to evaluate whether the speed of stent retrieval influences the recanalization and clinical outcome of patients presenting with the negative susceptibility vessel sign. MATERIALS AND METHODS: Patients were identified from a registry of patients with ischemic stroke receiving mechanical thrombectomy between January 2016 and January 2020. Inclusion criteria were the following: 1) acute ischemic stroke caused by an isolated occlusion of the anterior circulation involving the MCA (Internal Carotid Artery-L, M1, M2) within 8 hours of symptom onset; 2) a negative susceptibility vessel sign on prethrombectomy T2*-weighted images; and 3) treatment with a combined technique (stent retriever + contact aspiration). Patients were dichotomized according to retrieval speed (fast versus slow). The primary outcome was the first-pass recanalization rate. RESULTS: Of 68 patients who met inclusion criteria, 31 (45.6%) were treated with fast retrieval. Patients receiving a fast retrieval had greater odds of first-pass complete (relative risk and 95% confidence interval [RR 95% CI], 4.30 [1.80–10.24]), near-complete (RR 95% CI, 3.24 [1.57–6.68]), and successful (RR 95% CI, 2.60 [1.53–4.43]) recanalization as well as greater odds of final complete (RR 95% CI, 4.18 [1.93–9.04]), near-complete (RR 95% CI, 2.75 [1.55–4.85]), and successful (RR 95% CI, 1.52 [1.14–2.03]) recanalization. No significant statistical differences in procedure-related serious adverse events, distal embolization, or symptomatic intracranial hemorrhage were reported. No differences were noted in terms of functional independence (RR 95% CI, 1.01 [0.53–1.93]) and all-cause mortality (RR 95% CI, 0.90 [0.35–2.30]) at 90 days. CONCLUSIONS: A fast stent retrieval during mechanical thrombectomy is safe and improves the retrieval of clots with the negative susceptibility vessel sign.
Vitamin E Deficiency Disrupts Gene Expression Networks during Zebrafish Development

Vitamin E (VitE) is essential for vertebrate embryogenesis, but the mechanisms involved remain unknown. To study embryonic development, we fed zebrafish adults (>55 days) either VitE sufficient (E+) or deficient (E–) diets for >80 days, then the fish were spawned to generate E+ and E– embryos. To evaluate the transcriptional basis of the metabolic and phenotypic outcomes, E+ and E– embryos at 12, 18 and 24 h post-fertilization (hpf) were subjected to gene expression profiling by RNASeq. Hierarchical clustering, over-representation analyses and gene set enrichment analyses were performed with differentially expressed genes. E– embryos experienced overall disruption to gene expression associated with gene transcription, carbohydrate and energy metabolism, intracellular signaling and the formation of embryonic structures. mTOR was apparently a major controller of these changes. Thus, embryonic VitE deficiency results in genetic and transcriptional dysregulation as early as 12 hpf, leading to metabolic dysfunction and ultimately lethal outcomes.
Oxaliplatin-resistant colorectal cancer models for nanoparticle hyperthermia

Abstract Introduction Metastatic colorectal cancer (CRC) is complicated by chemotherapy-resistant cell populations. Oxaliplatin is used in heated intraperitoneal hyperthermic chemoperfusion (HIPEC) for treatment of disseminated CRC. Photothermal nanoparticles can provide focal heating to improve the response of CRC cells to oxaliplatin, by confining heating near individual cells. Reduction in cellular luciferase signal may allow single-cell-resolution recording of thermal dosimetry. Methods Oxaliplatin resistant (OxR) variants of luciferase-expressing CT26.WT-Fluc-Neo CRC cells were developed and their sensitivity to hyperthermia was evaluated. Polymer-based photothermal nanoparticles were developed, characterized and used to explore their potential for imparting a thermal dose to improve cell response to oxaliplatin. A correlation of thermal dose to intracellular luciferase activity was established using quantitative luminescence monitoring and microscopy. Results Luciferase-based monitoring of thermal dose within CT26 cell lines was validated within the ranges of 0.04–8.33 CEM43 for parental cells and 0.05–9.74 CEM43 for OxR CT26 cells. This was further confirmed using nanoparticle-induced hyperthermia, where the single-cell resolution of the thermal dose can be achieved. The nanoparticles enhance cell killing of resistant cells when combined with oxaliplatin and stimulated to generate heat. Conclusion Nanoparticle-based hyperthermia is effective for augmenting chemotherapy and can be coupled with reductions in CT26 luciferase expression to monitor thermal dose at single-cell resolution. The development of OxR CT26.WT-Fluc-Neo CRC cells sets the stage for pre-clinical evaluations to measure nanoparticle-induced hyperthermia to augment chemotherapy (Nano-HIPEC) in a chemotherapy-resistant model of disseminated CRC. Graphical Abstract
New pre-attachment Striga resistant sorghum adapted to African Agro-ecologies.

BACKGROUND Pre-attachment resistance to the parasitic plants Striga hermonthica and S. asiatica occurs in sorghum mutants designated low germination stimulant 1 (lgs1). However, only a few of these mutants have been identified and their resistance validated. Additionally, pre-attachment resistance in sorghum beyond lgs1 mutants has not been explored. We used lgs1 specific markers to identify new lgs1-like mutants in a diverse global sorghum collection. The sorghum collection was also evaluated for pre-attachment resistance against Striga using an in vitro assay that measured Striga germination activity and radicle growth. RESULTS Out of a total of 177 sorghum accessions, 60 recorded mean germination levels of below 42%, which is comparable to the previously identified lgs1-like sorghum (SRN39 and IS9830), used in this study as controls. Further, thirty-one of these accessions recorded Striga radicle lengths comparable, or lower than the controls (0.42 mm). Thirty-eight accessions contained the lgs1 mutation and although overall, lgs1 mutants had considerably reduced Striga germination, some low inducers of Striga germination were wild type for lgs1. Germination was positively but weakly correlated with radicle length pointing to additional radicle growth inhibitory activity. CONCLUSIONS Lgs1 mutations, alongside other mechanisms for low Striga germination stimulation, are prevalent in sorghum and poor Striga radicle growth is suggestive of host-derived inhibition. As an outcome, our study makes available multiple Striga resistant sorghum with adaptability to diverse agro-ecological regions in sub-Saharan Africa (SSA) making immediate deployment possible. This article is protected by copyright. All rights reserved.
State-of-the-Art Water Treatment in Czech Power Sector: Industry-Proven Case Studies Showing Economic and Technical Benefits of Membrane and Other Novel Technologies for Each Particular Water Cycle

The article first summarizes case studies on the three basic types of treated water used in power plants and heating stations. Its main focus is Czechia as the representative of Eastern European countries. Water as the working medium in the power industry presents the three most common cycles—the first is make-up water for boilers, the second is cooling water and the third is represented by a specific type of water (e.g., liquid waste mixtures, primary and secondary circuits in nuclear power plants, turbine condensate, etc.). The water treatment technologies can be summarized into four main groups—(1) filtration (coagulation) and dosing chemicals, (2) ion exchange technology, (3) membrane processes and (4) a combination of the last two. The article shows the ideal industry-proven technology for each water cycle. Case studies revealed the economic, technical and environmental advantages/disadvantages of each technology. The percentage of technologies operated in energetics in Eastern Europe is briefly described. Although the work is conceived as an overview of water treatment in real operation, its novelty lies in a technological model of the treatment of turbine condensate, recycling of the cooling tower blowdown plus other liquid waste mixtures, and the rejection of colloidal substances from the secondary circuit in nuclear power plants. This is followed by an evaluation of the potential novel technologies and novel materials.
Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp. , Aspergillus spp. , and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.