Induction Stage Research Articles

Observation of Art Therapy Relationships (OART): An observational tool for the research of therapist-client and client-artwork relationships in art therapy

Theories of art therapy cite the complex triangular relationship of this discipline that includes the therapist-client, client-artwork and therapist-artwork relationships. Yet, despite its importance, this triangular relationship has been insufficiently investigated. In this paper, we describe the development of a tool for the Observation of Art Therapy Relationships (OART) that assesses client-artwork and client-therapist interactions in art therapy based on conceptualizations of Attachment Theory. The development of the OART included three stages: a) An inductive stage in which researchers and experienced art therapists collaborated in defining observable phenomena that may shed light on the nature of the therapist-client and client-artwork relationships; b) A deductive stage, in which the phenomena defined in the inductive stage were incorporated into the structuring of an observational tool. 3. A qualitative examination of the OART in therapeutic settings. Challenges that have arisen and that may indicate the need for further work on the OART are discussed.

Environmental impact assessment of a novel third-generation biorefinery approach for astaxanthin and biofuel production

A novel third-generation biorefinery approach, including two paths of Ethanol/methane production pathway (EMP) and the direct methane production pathway (DMP), for astaxanthin and ethanol and biogas production from the freshwater microalgae Haematococcus pluvialis was developed previously. To ensure its environmental sustainability, a comprehensive life cycle assessment (LCA) study was conducted based on 1-GJ energy generation from biomethane as the functional unit. Results indicate that the EMP pathway had higher environmental impacts on all categories due to more stages and chemicals/energy consumption (at least five times greater effect). Results showed that while the enzymatic hydrolysis step followed by the fermentation stage was the main contributor to all environmental categories in the EMP route, astaxanthin induction dominated all environmental categories in the DMP route. The results showed that sodium nitrate, phosphate salts, inoculum sludge, acetone, and electricity had considerable environmental impacts. Moreover, despite low enzyme usage in enzymatic hydrolysis, these proteins significantly impacted all environmental categories in this stage. The baseline analysis concluded that to produce 1 GJ energy from methane, about 88 kg and 13 kg CO2 were generated from the EMP and DMP pathways, respectively. A sensitivity analysis was also conducted to compare various ratios of chemicals, such as phosphate salts, with high contributions to enzymatic hydrolysis and astaxanthin induction stages in the EMP and DMP routes, respectively. Finally, the LCA results revealed that the DMP pathway is more environmentally friendly with the same economic value of biomethane and astaxanthin production. This LCA study updated the data related to the environmental assessment of processes to utilize H. pluvialis to produce biofuels and astaxanthin simultaneously.

Unexpected Differences in the Speed of Non-Malignant versus Malignant Cell Migration Reveal Differential Basal Intracellular ATP Levels

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared with normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate, utilizing several cell lines from the breast and lung. Initial screening was performed in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of the growth media used. Given the paradigm-shifting nature of our discovery, we pursued the mechanisms that could be responsible. Neither mass, cell doubling, nor volume accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of intracellular ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased intracellular ATP at premigratory-wound induction, but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

The Correlation between Fetal Monitor Decelerations Area and Neonatal Cord pH among Preeclamptic parturient: an Automated Approach to a Clinical Challenge.

To examine whether a correlation exists between electronic fetal monitoring (EFM) in the final 120 minute prior to delivery and neonatal cord blood pH among parturients with preeclampsia. A retrospective cohort study of parturients with term and near-term preeclampsia who delivered at Soroka University Medical Center between 2013 and 2020 was conducted. EFM tracings, demographical data, and obstetrical outcomes were retrieved from the patients' electronic medical records. Using MATLAB program, area under the curve (AUC) measurements were applied. Correlation was calculated using the Spearman's correlation coefficient. EFM of 88 parturients with preeclampsia were assessed. A significant negative correlation was demonstrated between cord blood pH and the decelerations AUC, total decelerations duration, and deceleration depth. No correlation was demonstrated between area over the curve (acceleration) and cord blood pH. In a multivariate linear regression, total deceleration AUC was found independently negatively associated with cord blood pH (beta = -0.264, p = 0.011) controlling for second stage of labor duration and induction of labor. Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia. Further studies are needed to strengthen and establish the use of electronic EFM in the management of labor and delivery. · A negative correlation was demonstrated between cord blood pH and the decelerations AUC.. · Total deceleration AUC was found independently negatively associated.. · Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia..

JUNB affects hair follicle development and regeneration by promoting the proliferation of dermal papilla cells in goat

Abstract Background The process of hair follicle morphogenesis, development, and regeneration essentially depends on the interaction between skin epidermis and dermis, while dermal papilla (DP) cells play a vital role in this process. Transcription factors recognize specific DNA sequences to regulate gene transcription during hair follicle development. Our previous sequencing data have demonstrated that JUNB is differentially expressed between the induction and differentiation stages during hair follicle development of cashmere goat. However, the underlying mechanism of JUNB currently remains unknown. Results The function of JUNB on DP cells was explored by EdU, MTT, CCK-8, and flow cytometry analysis, which showed that JUNB significantly promoted the cell viability and proliferation. Subsequently, the underlying regulation mechanism of JUNB was investigated. The dual-luciferase reporter assay and RT-qPCR results revealed that TCF3 was a target gene of JUNB. And the expressions of Wnt signaling pathway-related genes, CTNNB1 (β-catenin), Cyclin D1, and C-myc, were significantly promoted at mRNA and protein levels. The homology analysis based on JUNB protein sequences revealed that goat and mouse had high homology among 11 species. Therefore, C57 BL/6 mice were selected as the animal model for further in vivo experiment. The result showed that JUNB promoted hair regeneration of mouse, and the HE and immunofluorescence staining results of skin tissues further proved it. Conclusions Taken together, our results revealed that JUNB promoted the proliferation of DP cells by regulating Wnt signaling pathway, thereby affecting hair regeneration, which would provide molecular target for improving cashmere quality and breeding of cashmere goats. Graphical Abstract

Exogenous arginine promotes the coproduction of biomass and astaxanthin under high-light conditions in Haematococcus pluvialis

The economical way of Haematococcus pluvialis farming is to simultaneously achieve biomass, astaxanthin and lipid using less expensive chemicals. This paper explores the role of exogenous arginine in promoting growth and astaxanthin accumulation under stressful conditions. The application of arginine exerts a synergic effect on biomass, astaxanthin and lipid by improving carbon utilization, activating the arginine pathway and regulating carotenoid and lipid-related genes. Genes related to arginine catabolism, such as ADC, OCT, ASS1, NOS, and OAT, were up-regulated at both the cultivation and astaxanthin induction stages, signifying their importance in both growth and astaxanthin synthesis. Furthermore, transcriptome analysis revealed that arginine up-regulated transcription levels of genes involved carbon fixing, lipid biosynthesis, pyruvate metabolism, carotenoid, tricarboxylic acid cycle, and arginine and proline metabolism. The results provide a significant mechanism and applicability of using exogenous arginine and high light to stimulate bioproducts from Haematococcus pluvialis.

UPAYA KEGIATAN MUHAFADHOH DALAM MENINGKATKAN HAFALAN NADZOM IMRITI PADA MURID KELAS 4 MI MIFTAHUL HUDA

This study aims to find out 1) how the muhafadhoh activities are carried out and 2) how much muhafadhoh activities are in improving the memorization of nadzom imriti in 4th grade students of MI Miftahul Huda. This research uses qualitative research with the type of case study research. This research was conducted directly in the field, observing directly and seeking information from direct informants. The data in this study were taken from observations, interviews, and documentation. The data analysis of this research went through the inductive analysis stage, which started its analysis from emotional facts not from theory. The results of this study are seen from the results of observations and interviews with several students, this muhafadhoh activity can really help improve the memorization of nadzom imriti in 4th grade students of MI Miftahul Huda. This result can be seen from the confessions of the interviewed students, they really felt the positive impact of the muhafadhoh activity. So they can memorize more easily than usual. This activity is also really helpful in passing the memorization test that they must pass at the end of each school year.

Plant Regeneration via Organogenesis in Jerusalem Artichokes and Comparative Analysis of Endogenous Hormones and Antioxidant Enzymes in Typical and Atypical Shoots.

The Jerusalem artichoke (Helianthus tuberosus) is a tuberous plant with considerable nutrient and bioactive compounds. The optimization of the in vitro clonal propagation protocol is critical for large-scale reproduction and biotechnological applications of Jerusalem artichoke production. In this work, in vitro plant regeneration from the stem nodes of the Jerusalem artichoke via direct organogenesis is presented. In the shoot induction stage, the stem segments produced more shoots with vigorous growth on MS medium containing 0.5 mg/L 6-benzylaminopurine (6-BA). The concentrations of 6-BA and gibberellic acid (GA3) were both optimized at 0.5 mg/L for shoot multiplication, and the combination of 0.05 mg/L indole-3-butyric acid (IBA) and 0.05 mg/L 1-naphthylacetic acid (NAA) was the most responsive for root induction, yielding the largest number of roots. The regenerated plantlets were successfully hardened at a 96% survival rate and vigorously grew in the field. The genetic stability of the regenerated plants was confirmed by flow cytometry and simple sequence repeat (SSR) analysis. However, 17.3% of shoots on the optimum shoot induction medium had withered leaves and excessive callus (atypical shoots), which greatly reduced the induction efficiency. Enzyme activity in the typical and atypical shoots was compared. The atypical shoots had significantly higher levels of endogenous indole-3-acetic acid (IAA) and abscisic acid (ABA), as well as increased activity of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), whereas the content of 6-BA, zeatin (ZT), and GA3 was significantly reduced. The activity of the three enzymes was positively correlated with the content of IAA and ABA, while being negatively correlated with that of 6-BA, ZT, and GA3. The results suggest that the poor growth of the atypical shoots might be closely related to the significant accumulation of endogenous IAA and ABA, thus significantly increasing antioxidant enzyme activity.

Transplantation of autologous bone marrow–derived mononuclear cells into cerebrospinal fluid in a canine model of spinal cord injury

IntroductionSpinal cord injury (SCI) is associated with severe dysfunction of nervous tissue, and repair via the transplantation of bone marrow–derived mononuclear cells (BM-MNCs) into cerebrospinal fluid yields promising results. It is essential to understand the underlying mechanisms; therefore, this study aimed to evaluate the regenerative potential of autologous BM-MNC transplantation in a canine model of acute SCI. MethodsSix dogs were included in this study, and SCI was induced using an epidural balloon catheter between L2 and L3, particularly in the area of the anterior longitudinal ligament. BM-MNC transplantation was performed, and T2-weighted magnetic resonance imaging (MRI) was conducted at specific time points (i.e., immediately after inducing SCI and at 1, 2, and 4 weeks after inducing SCI); moreover, the expression of growth-associated protein 43 (GAP-43) was evaluated. ResultsMRI revealed that the signal intensity reduced over time in both BM-MNC–treated and control groups. However, the BM-MNC–treated group exhibited a significantly faster reduction than the control group during the early stages of SCI induction (BM-MNC–treated group: 4.82 ± 0.135 cm [day 0], 1.71 ± 0.134 cm [1 week], 1.37 ± 0.036 cm [2 weeks], 1.21 cm [4 weeks]; control group: 4.96 ± 0.211 cm [day 0], 2.49 ± 0.570 cm [1 week], 1.56 ± 0.045 cm [2 weeks], 1.32 cm [4 weeks]). During the early stages of treatment, GAP-43 was significantly expressed at the proximal end of the injured spinal cord in the BM-MSC–treated group, whereas it was scarcely expressed in the control group. ConclusionsIn SCI, transplanted BM-MNCs can activate the expression of GAP-43, which is involved in axonal elongation (an important process in spinal cord regeneration). Thus, cell therapy with BM-MNCs can provide favorable outcomes in terms of better regenerative capabilities compared with other therapies.

When Patients with Plasma Cell Disorders Encountered the Largest Omicron Wave (December 2022) in China: A Real-World Multicenter and Multiregional Study

Background: An unprecedented nationwide Omicron outbreak hit China in December 2022. Patients with plasma cell disorders have been confirmed to exhibit worse outcomes following COVID-19 infection, although data on the impact of Omicron on this population in China remain scarce. This study aims to report the clinical and epidemiological characteristics of plasma cell disorder patients during this major Omicron outbreak. It also analyzes the association between patient clinical characteristics and clinical course (infection, severity, hospitalization, and time to recovery) of COVID-19. Methods: We performed a multicenter and multiregional retrospective study primarily involving nine large tertiary hematology centers across nine provinces/cities in China. The study period was limited to December 1 st, 2022 - January 19 th, 2023. A total of 404 plasma cell disorder patients participated in the survey. Results: During follow-up, 342 patients had a laboratory or clinical diagnosis of COVID-19. The prevalence of COVID-19 within the study population was 76.2%. Among those with COVID-19, the majority were with multiple myeloma (325, 95.0%), and over half (201, 58.8%) were unvaccinated. At the time of COVID-19, 121 (40.1%) patients were undergoing maintenance therapy. Ninety (31.3%) patients had prior exposure to anti-CD38 monoclonal antibody, while 25 (8.7%) to CAR-T. The rates of severe illness and hospitalization were 16.4% and 20.5%, respectively. Four (5.7%) patients required ICU support and only two (2/277, 0.7%) deaths were reported. As of the data cutoff date (January 19 th, 2023), 231 (231/277, 83.4%) patients had recovered from COVID-19, with a median time to recovery of 14 days (95% CI: 13-15 days). Multivariate analysis identified age > 65 (OR 1.47, 95% CI 1.05-2.05, P = 0.02) and anti-CD38 monoclonal antibody within six months of COVID-19 (OR 1.47, 95% CI 1.03-2.09, P = 0.03) as independent risk factors for severe COVID-19 illness. Prior CAR-T therapy within six months was correlated with an increased risk of hospitalization (OR 3.49, 95% CI 1.07-11.4, P = 0.04) and prolonged time to recovery (HR 0.38, 95% CI 0.16-0.93, P = 0.03). Compared to maintenance therapy, patients at the induction or consolidation therapy stage had an elevated risk of hospitalization following COVID-19 (OR 1.55, 95% CI 1.04-2.33, P = 0.03). Notably, no significant protective effect of COVID-19 vaccination on infection or severe infection rates was observed ( P > 0.05). Conclusions: Although the impact of Omicron appears attenuated in plasma cell disorder patients, this vulnerable population still exhibits higher rates of severe illness and poorer outcomes compared to the general population. Apart from known risk factor (i.e. older age), certain treatment-related factors, including induction/consolidation therapy stage, recent anti-CD38 monoclonal antibody exposure, and prior CAR-T therapy, are associated with increased risks of severe COVID-19, hospitalization, and prolonged time to recovery. However, the protective effect of vaccination against COVID-19 is not identified. The findings from this work provide implications for the clinical management of PCD patients during the pandemic under the likely scenario of future resurgences of COVID-19.

The Choice Study, Cervical Ripening In-Hospital and At-Home: Qualitative Findings and Implications for Practice

Cervical ripening (CR) is recommended as the first stage of induction of labour (IOL) in most circumstances.1 The procedure involves application of an agent, either pharmaceutical such as Prostin, or mechanical, including balloon catheter or osmotic dilator, with the aim of softening and shortening the cervix in preparation for labour. Traditionally, CR has taken place in hospital. However, some UK maternity units now offer the opportunity to return home for a period after application of the cervical ripening agent, referred to as home CR.

Assessment of the management and outcome of neutropenia in paediatric haemato-oncology inpatients at Kenyatta National Hospital

Background: Neutropenia is a common complication among the haemato-oncology pediatric patients. Children who develop such complications are prone to bacterial infections which further predispose them to death. This study aimed at improving the practice of management of neutropenia in children with the view of reducing pediatric haemato-oncology mortality. Methods: We retrospectively reviewed medical records of paediatric haemato-oncology inpatients aged 13 years and below, who developed neutropenia during treatment at Kenyatta National Hospital. A data abstraction form was used to collect data from 113 medical records of patients admitted between 1st January 2020 and 31st December 2020. Data were analyzed using R to obtain descriptive and inferential statistics using a 95% confidence interval. Results: Boys constituted most of the cases assessed. The median (IQR) age at admission was 6 (4, 10) years. Leukaemias were more common than lymphomas. Acute lymphocytic leukaemia (59%) and Hodgkin’s lymphoma (4%) were the most and least frequently diagnosed haemato-oncology cancers. Most patients were diagnosed during the induction stage, 47 (42%) and had febrile neutropenia 59 (52%). Vaccination and bone marrow suppression histories were poorly documented. Thirty-three (29%) patients were reported to have succumbed during their treatment. G-CSF prescription was statistically significantly associated (p=0.045) with the survival status (death or alive) of patients, particularly at the induction stage (p=0.007). Conclusions: Neutropenia management in KNH is done as per protocol, with room to improve on history taking. Although 29% of the children succumbed within the course of treatment, the majority (71%) of the patients were discharged.

Effect of spermidine, glutamine, and proline on somatic embryogenesis and silver nanoparticles supplied culture improved rhizome formation of Panax vietnamensis var. langbianensis

Lang Bian ginseng (Panax vietnamensis var. langbianensis) is a rare and traditional herbal medicine with many pharmacological activities. It was first discovered by Duy et al. (2016) in Lam Dong province, Vietnam. Until now, there has been only one publication on Lang Bian ginseng micropropagation via somatic embryogenesis (Anh et al., 2022). However, this study still had limitations, including the small number of somatic embryos and the time-consuming. This study investigated the effect of spermidine, glutamine, and proline on the enhancement of somatic embryogenesis (SE) of Lang Bian ginseng using thin cell layer culture technology. The results showed that the optimal SE rate and the number of somatic embryos per explant were achieved on MS medium supplemented with 0.01 mM spermidine in leaf explants (93.32 % and 54.20 embryos, respectively) and petiole explants (96.66 % and 68.80 embryos, respectively) and higher compared to these in other treatments, including control, glutamine, and proline treatments. Besides, adding 0.01 mM spermidine to the culture medium also improved the quality of somatic embryos, mainly cotyledonary stage, through an enhanced synthesis of antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD), and ascorbate peroxidase (APX)]. In addition, the fluctuations of endogenous hormones during initiation and maturation of SE derived from 0.01 mM spermidine treatment were recorded. Endogenous CKs (ZEA, 2iP, KIN, mT), IAA, and GA3 concentrations were the highest during the induction stage in both explants. Meanwhile, the remaining endogenous hormones (MEL, ABA, and SA) exhibited no inevitable fluctuation trends. In addition, IAA was only detected at the induction stage of SE in both explants. Moreover, cotyledonary somatic embryos derived from 0.01 mM spermidine treatment grew well in MS medium supplemented with 1.2 mg/L AgNPs.

A Mathematical Model for a Hybrid Ignition System

In the operation of a car's ignition system, the primary ignition coil is responsible for generating a high voltage that typically ranges from around 100V to 300V. However, this self-induced electromotive force (emf) can lead to certain negative effects such as switch breakdown, inductive noise, and secondary voltage drop. This article introduces a novel hybrid ignition system designed for a 4-cylinder engine. This innovative system is a combination of capacitive discharge ignition system (CDI) and induction discharge ignition (IDI) system. The excess electromagnetic force energy (emf) generated during the induction ignition stage will be used in the capacitive ignition. Thereby contributing to limiting the negative effects as mentioned. Forming and solving the mathematical model for the hybrid ignition system mentioned above enables us to analyze the transient responses of the primary current (i1) and primary voltage (V1). These instantaneous responses are crucial in understanding the behavior of the composite ignition circuit and calculating key parameters such as ignition energy during the inductive and capacitive ignition stages, as well as the magnitude of the maximum secondary voltage (V2m). Furthermore, the article also presents experimental results from the hybrid ignition system to complement the theoretical analysis.

A crosslinking kinetic model considering reversion effect with verification and its application in thick rubber vulcanization process

Vulcanization is crucial for rubber product processing. The phenomenon of “over-cure on the outside surface and under-cure at the inside position” often occurs for thick rubber products; however, very few suitable kinetic models exist to describe the reversion stage of rubber curing under non-isothermal conditions currently. In this study, we proposed a piecewise nonlinear crosslinking kinetic model that could reproduce the kinetic responses of three vulcanization stages (induction, curing, and reversion stage). A thick rubber sphere with a diameter of 50 mm was utilized to verify the accuracy of the crosslinking kinetic model. The test data distribution of temperature and crosslinking density at different points of the rubber sphere were measured using thermocouples and low-field nuclear magnetic resonance tester, respectively. The crosslinking kinetic model was implemented with user-defined subroutines in Abaqus/Standard (UVARM and USDFLD). The distribution of temperature and degree of curing of the rubber sphere were simulated. Comparison between test data and simulation data indicated that the proposed piecewise nonlinear crosslinking kinetic model can predict the rubber vulcanization kinetic behavior under both isothermal and non-isothermal conditions, which can help design and optimize the vulcanization process for thick rubber articles.

Propofol TCI or sevoflurane anesthesia without muscle relaxant for thoracoscopic thymectomy in myasthenia gravis patients: a prospective, observational study

BackgroundMyasthenia gravis (MG) patients interact unpredictably with anesthetic agents, including neuromuscular blocking agents. Here, we investigate the effectiveness of general anesthesia without muscle relaxants using either propofol via target-controlled infusion systems (TCI) or sevoflurane in MG patients undergoing thoracoscopic thymectomy.MethodsThis prospective, open-label, observational study was conducted in a university hospital. We included 90 myasthenic patients undergoing thoracoscopic thymectomy with general anesthesia. Patients received induction and maintenance anesthesia with propofol TCI (group P, n = 45) or induction with propofol 2–3 mg.kg−1 and maintenance anesthesia with sevoflurane (group S, n = 45). In both groups, the procedure was performed under the guidance of entropy with sufentanil but not a muscle relaxant. Intubation conditions, hemodynamic changes, respiratory function, neuromuscular transmission, arterial blood gas, and complications were evaluated.ResultsAll patients achieved good intubation conditions. Hemodynamic instability was more frequent in group S than in group P, mostly in the induction stage, and was controllable. The reduction in the intraoperative train-of-four ratio from baseline at 30 min, 60 min, and 90 min in group S was 10.3%, 14.2%, and 14.3%, respectively, significantly higher than that in group P (6.8%, 7.2%, and 8.4%, respectively), which completely recovered at the end of the surgery. All patients were extubated in the operating room without complications. No other significant differences between the groups were observed.ConclusionsAnesthesia with propofol TCI or sevoflurane without muscle relaxants in MG patients offered safe and effective conditions for thoracoscopic thymectomy. Sevoflurane achieved higher levels of intraoperative muscular relaxation than propofol TCI. Postoperative neuromuscular function was not affected by these anesthetics.

Development of a continuous fermentation process for the production of recombinant uricase enzyme by Pichia pastoris.

Recent studies in the biopharmaceutical industry have shown an increase in the productivity and production efficiency of recombinant proteins by continuous culture. In this research, a new upstream fermentation process was developed for the production of recombinant uricase in the methylotrophic yeast Pichia pastoris. Expression of recombinant protein in this system is under the control of the AOX1 promoter and therefore requires methanol as an inducing agent and carbon/energy source. Considering the biphasic growth characteristics of conventional fed-batch fermentation, physical separation of the growth and induction stages for better control of the continuous fermentation process resulted in higher dry-cell weight (DCW) and enhanced recombinant urate oxidase activity. The DCW and recombinant uricase activity enzyme for fed-batch fermentation were 79g/L and 6.8u/mL. During the continuous process, in the growth fermenter at a constant dilution rate of 0.025h-1 , DCW increased to 88.39g/L. In the induction fermenter, at methanol feeding rates of 30, 60, and 80mL/h, a recombinant uricase activity was 4.13, 7.2, and 0u/mL, respectively. The optimum methanol feeding regime in continuous fermentation resulted in a 4.5-fold improvement in productivity compared with fed-batch fermentation from 0.04u/mL/h (0.0017mg/mL/h) to 0.18u/mL/h (0.0078mg/mL/h).

Clinical value of serum interleukin-13 levels in vincristineinduced polyneuropathy in children with acute lymphoblastic leukemia

Vincristine polyneuropathy is the leading neurotoxic effect when treating pediatric acute lymphoblastic leukemia (ALL). Recent studies have demonstrated involvement of immune system in pathogenesis of peripheral nervous system damage. Over recent years, there have been reports examining the relationship between interleukin-13 (IL-13) and development of toxic effects of chemotherapeutic drugs. Our objective was to assess clinical value of IL-13 level in children with vincristine polyneuropathy. The study included 27 children with ALL aged from 3 to 17 years, who received chemotherapy according to the conventional protocol. Plasma IL-13 levels were determined, and the values in two subgroups have been compared taking into account development of vincristine polyneuropathy. IL-13 content was assessed by multiparametric immunofluorescent analysis with magnetic microspheres (xMAP technology, Luminex 200, USA) and using ProcartaPlex Human Cytokine/Chemokine test system (Invitrogen, USA). Vincristine polyneuropathy in the study group was registered in the majority of children (n = 15) manifesting mainly at the induction stage of chemotherapy and presenting as predominance of sensory disorders. In a comparative analysis of IL-13 plasma levels in patients with vincristine polyneuropathy, we observed a statistically significant increase of its concentration, in contrast to patients without signs of peripheral nervous system damage (p = 0.042). The diagnostic sensitivity of this index was 75%, specificity – 100%, the integral index characterizing the accuracy of the test was 0.89. IL-13 changes were found to correlate with higher relative risk level, indicating its significant relationship to the development of vincristine polyneuropathy. The results of the study on the IL-13 content in blood plasma in children with vincristine polyneuropathy allowed us to consider it a predictive biological marker of peripheral nervous system damage.

Mechanism of transforming growth factor-β1 inducing renal fibrosis based on transcriptome sequencing analysis.

To explore the mechanism of transforming growth factor-β1 (TGF-β1) inducing renal fibrosis. Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used to analyze the sequencing results. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened in differentially expressed genes. Then, the expression of these genes during renal fibrosis were verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and data set GSE104954 in high-throughput gene expression database. After TGF-β1 treatment for 6, 12, and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes of differential expression were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes of Hippo, TGF-β and Wnt signaling pathways were mainly manifested, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in cell model showed that TGF-β1 induced 9 transcription factors expressions (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not change significantly after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation in the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. TGF-β1 induces genes differentially expressed in renal fibroblasts, and Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.

How meningeal macrophages control medulloblastoma induction.

In this issue of Developmental Cell, Pokrajac etal. report that Wnt signaling in endothelial cells maintain CXCL4 expression in meningeal macrophages, which suppresses induction of Sonic hedgehog medulloblastoma by antagonizing the pro-tumor effects of CXCL12. This work highlights how homeostatic tissue macrophages can regulate early stages of tumor induction.