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BackgroundMinimizing the duration of mechanical ventilation is one of the most important therapeutic goals during the care of preterm infants at neonatal intensive care units (NICUs). The rate of extubation failure among preterm infants is between 16% and 40% worldwide. Numerous studies have been conducted on the assessment of extubation suitability, the optimal choice of respiratory support around extubation, and the effectiveness of medical interventions. Since the Caffeine Therapy for Apnea of Prematurity (CAP) trial, caffeine has become one of the essential drugs at NICUs. However, the optimal dosage and timing for adequate effectiveness still need to be more conclusive. Previous studies suggest that higher doses of caffeine treatment increase the success rate of extubation. Therefore, we aim to determine whether using a single additional loading dose of caffeine citrate one hour prior to extubation impacts the success rate of extubation.MethodsThe study is an open-label, multicenter randomized clinical trial testing the effectiveness and safety of pre-extubational loading dose of caffeine citrate. Inclusion criteria will be infants born before the 32nd gestational week, before the first extubation attempt after at least 48 hours of mechanical ventilation, and a signed parental informed consent. A total of 226 patients will be randomly allocated to either the experimental or control group. The randomization will be stratified by gestational age and antenatal steroid prophylaxis. Preterm infants in the experimental group will receive an additional intravenous (IV) loading dose (20 mg/kg) of caffeine citrate one hour before the first planned extubation, in addition to the standard dosing regimen (20 mg/kg caffeine citrate IV on the first day of life and 5 to 10 mg/kg IV or orally caffeine citrate each consecutive day). Preterm infants in the control group will receive the standard dosing regimen. The primary outcome will be reintubation within 48 hours.DiscussionA pre-extubational loading dose of caffeine citrate can reduce extubation failure. Obtaining evidence on this feature has the potential to contribute to finding the optimal dosing regimen.Trial registration numberThe study protocol was approved by the Hungarian Ethics Committee for Clinical Pharmacology of the Medical Research Council and National Institute of Pharmacy and Nutrition (OGYÉI/6838-11/2023). ClinicalTrials.gov identifier NCT06401083 Registered 06. May 2024.; EudraCT number: 2022-003202-77.

Background: Minimizing the duration of mechanical ventilation is one of the most important therapeutic goals during the care of preterm infants at neonatal intensive care units (NICUs). The rate of extubation failure among preterm infants is between 16% and 40% worldwide. Numerous studies have been conducted on the assessment of extubation suitability, the optimal choice of respiratory support around extubation, and the effectiveness of medical interventions. Since the Caffeine Therapy for Apnea of Prematurity (CAP) trial, caffeine has become one of the essential drugs at NICUs. However, the optimal dosage and timing for adequate effectiveness still need to be more conclusive. Previous studies suggest that higher doses of caffeine treatment increase the success rate of extubation. Therefore, we aim to determine whether using a single additional loading dose of caffeine citrate one hour prior to extubation impacts the success rate of extubation. Methods: The study is an open-label, multicenter randomized clinical trial testing the effectiveness and safety of pre-extubational loading dose of caffeine citrate. Inclusion criteria will be infants born before the 32nd gestational week, before the first extubation attempt after at least 48 hours of mechanical ventilation, and a signed parental informed consent. A total of 226 patients will be randomly allocated to either the experimental or control group. The randomization will be stratified by gestational age and antenatal steroid prophylaxis. Preterm infants in the experimental group will receive an additional intravenous (IV) loading dose (20 mg/kg) of caffeine citrate one hour before the first planned extubation, in addition to the standard dosing regimen (20 mg/kg caffeine citrate IV on the first day of life and 5 to 10 mg/kg IV or orally caffeine citrate each consecutive day). Preterm infants in the control group will receive the standard dosing regimen. The primary outcome will be reintubation within 48 hours. Discussion: A pre-extubational loading dose of caffeine citrate can reduce extubation failure. Obtaining evidence on this feature has the potential to contribute to finding the optimal dosing regimen. Trial registration number: The study protocol was approved by the Hungarian Ethics Committee for Clinical Pharmacology of the Medical Research Council and National Institute of Pharmacy and Nutrition (OGYÉI/6838-11/2023). ClinicalTrials.gov identifier NCT06401083 Registered 06. May 2024.; EudraCT number: 2022-003202-77. [ABSTRACT FROM AUTHOR]

The nondestructive determination of the neutron-irradiation-induced embrittlement of nuclear reactor pressure-vessel steel is a very important and recent problem. Within the scope of the so-called NOMAD project funded by the Euratom research and training program, novel nondestructive electromagnetic testing and evaluation (NDE) methods were applied to the inspection of irradiated reactor pressure-vessel steel. In this review, the most important results of this project are summarized. Different methods were used and compared with each other. The measurement results were compared with the destructively determined ductile-to-brittle transition temperature (DBTT) values. Three magnetic methods, 3MA (micromagnetic, multiparameter, microstructure and stress analysis), MAT (magnetic adaptive testing), and Barkhausen noise technique (MBN), were found to be the most promising techniques. The results of these methods were in good agreement with each other. A good correlation was found between the magnetic parameters and the DBTT values. The basic idea of the NOMAD project is to use a multi-method/multi-parameter approach and to focus on the synergies that allow us to recognize the side effects, therefore suppressing them at the same time. Different types of machine-learning (ML) algorithms were tested in a competitive manner, and their performances were evaluated. The important outcome of the ML technique is that not only one but several different ML techniques could reach the required precision and reliability, i.e., keeping the DBTT prediction error lower than a ±25 °C threshold, which was previously not possible for any of the NDE methods as single entities. A calibration/training procedure was carried out on the merged outcome of the testing methods with excellent results to predict the transition temperature, yield strength, and mechanical hardness for all investigated materials. Our results, achieved within the NOMAD project, can be useful for the future potential introduction of this (and, in general, any) nondestructive evolution method. [ABSTRACT FROM AUTHOR]

A novel nondestructive method called magnetic adaptive testing has been previously applied to detect the neutron-irradiation-generated structural changes in reactor pressure vessel steel material. This method has been found to be a useful tool for this purpose, and good correlation—as a tendency—has been found between the estimated ductile-to-brittle transition temperature and magnetic parameters. However, a significant scattering of measured points was also observed for the investigated set of Charpy specimens. The main result of the work was that by magnetic selection of samples, the scatter can be notably reduced. As a conclusion, the magnetically measured parameters seemed to be precise and reliable for the detection of embrittlement of the reactor pressure vessel steel, with lower scattering of points than in the conventionally used destructive mechanical characteristics (ductile-to-brittle transition temperature). This result is surprising and needs further verification. The purpose of the present work is to repeat the measurement on irradiated reactor steel blocks. In this work, instead of the DBTT transition temperature, individually measured Vickers hardness (VH) data were used to help characterize the mechanical properties of the material. The so-called “property transformation” is a known and applied technique in the nuclear industry. The mechanical property characterized by the transition temperature cannot be determined individually for each specimen; instead, it can be obtained only on a set of samples by statistical fitting. Therefore, the individually measured Vickers hardness values can be utilized in order to predict the individual transition temperature values by the help of the property transformation technique. In this paper, however, not these derived transition temperature values, but their origins, the Vickers hardness values, are studied in a direct manner. The same behavior of blocks was observed as in the case of Charpy specimens, which is considered to validate the previously published results. As a possible reason for the scattering of points, large magnetic inhomogeneity of samples cut even from the same block was also proved. The magnetic parameters and Vickers hardness correlate well with each other. This result justifies the potential future application of magnetic techniques in practice aimed at the regular inspection of nuclear reactors.

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Surface quality measures such as roughness, and especially its uncertain character, affect most magnetic non-destructive testing methods and limits their performance in terms of an achievable signal-to-noise ratio and reliability. This paper is primarily focused on an experimental study targeting nuclear reactor materials manufactured from the milling process with various machining parameters to produce varying surface quality conditions to mimic the varying material surface qualities of in-field conditions. From energising a local area electromagnetically, a receiver coil is used to obtain the emitted Barkhausen noise, from which the condition of the material surface can be inspected. Investigations were carried out with the support of machine-learning algorithms, such as Neural Networks (NN) and Classification and Regression Trees (CART), to identify the differences in surface quality. Another challenge often faced is undertaking an analysis with limited experimental data. Other non-destructive methods such as Magnetic Adaptive Testing (MAT) were used to provide data imputation for missing data using other intelligent algorithms. For data reinforcement, data augmentation was used. With more data the problem of ‘the curse of data dimensionality’ is addressed. It demonstrated how both data imputation and augmentation can improve measurement datasets.

The influence of neutron irradiation degradation on reactor pressure vessel steel was investigated. Large blocks were irradiated by neutrons in the BR2 reactor at a low irradiation temperature. They were measured by a nondestructive magnetic method, magnetic adaptive testing, before and after the neutron irradiation. It was shown that the modification of the magnetic parameters due to the neutron irradiation was well detectable by this nondestructive method. It was also shown that the influence of neutron irradiation could be detected with a reasonable signal-to-noise ratio through the cladding. The present results are considered as a first step towards the application of magnetic adaptive testing in the nuclear industry.

Back in 1995, a landmark paper was published, which shaped the fibrosis literature for many years to come. During the characterization of a fibroblast-specific marker (FSP1) in the kidneys, an observation was made, which gave rise to the hypothesis that “fibroblasts in some cases arise from the local conversion of epithelium.” In the following years, epithelial-mesenchymal transition was in the spotlight of fibrosis research, especially in the kidney. However, the hypothesis came under scrutiny following some discouraging findings from lineage tracing experiments and clinical observations. In this review, we provide a timely overview of the current position of the epithelial-mesenchymal transition hypothesis in the context of fibrosis (with a certain focus on renal fibrosis) and highlight some of the potential hurdles and pitfalls preventing therapeutic breakthroughs targeting fibrotic epithelial-mesenchymal transition.

Neutron irradiation-generated embrittlement of nuclear pressure vessel steel was inspected by a nondestructive magnetic method, called magnetic adaptive testing (MAT). This method is based on systematic measurement and evaluation of minor magnetic hysteresis loops. Result of MAT measurement was compared with the result of the traditional Charpy measurement. Good correlation was found between these parameters. One of the main findings of the present work is that the considerable part of scatter of points obtained by magnetic measurement can be attributed to local material inhomogeneity. Another important conclusion is that the embrittlement highly depends on the initial local material conditions, i.e., the initial microstructure, which are very different even within the same block of reactor steel material. By taking this into account, the magnetic descriptors obtain more precise determination of the local embrittlement than the traditionally used destructive mechanical parameters from Charpy data.

The embrittlement of two types of nuclear pressure vessel steel, 15Kh2NMFA and A508 Cl.2, was studied using two different methods of magnetic nondestructive testing: micromagnetic multiparameter microstructure and stress analysis (3MA-X8) and magnetic adaptive testing (MAT). The microstructure and mechanical properties of reactor pressure vessel (RPV) materials are modified due to neutron irradiation; this material degradation can be characterized using magnetic methods. For the first time, the progressive change in material properties due to neutron irradiation was investigated on the same specimens, before and after neutron irradiation. A correlation was found between magnetic characteristics and neutron-irradiation-induced damage, regardless of the type of material or the applied measurement technique. The results of the individual micromagnetic measurements proved their suitability for characterizing the degradation of RPV steel caused by simulated operating conditions. A calibration/training procedure was applied on the merged outcome of both testing methods, producing excellent results in predicting transition temperature, yield strength, and mechanical hardness for both materials.

The influence of surface roughness on magnetic measurements of Reactor Pressure Vessel Steels was investigated by applying two types of magnetic, non-destructive measurement on nuclear reactor pressure vessel steel samples: magnetic adaptive testing (MAT) and magnetic Barkhausen noise measurement (MBN). The surface roughness was modified by primary and secondary machine cutting forces. Different settings of machine cutting produced different surface conditions. It was found that for both measurements a monotonic correlation was found to exist between magnetic parameters and surface roughness. Results of the MAT measurements found that the correlation depends on the speed (i.e., on the applied slew rate) of the magnetizing current. In a similar fashion, results from the MBN method show good agreement with MAT, where the response diminishes with an increase in surface roughness. The results show the importance of accounting for surface condition in the interpretation of results of non-destructive magnetic testing.

The neutron irradiation embrittlement of four different types of nuclear pressure vessel materials (three base metals and one weld material) were investigated by a magnetic nondestructive testing method, magnetic adaptive testing (MAT). The method is based on the measurement of minor magnetic hysteresis loops on Charpy specimens irradiated by neutrons in the BR2 reactor. Due to the neutron irradiation, the structure of the material was modified. The Charpy impact method is suitable for destructive characterization of material embrittlement. The results of Charpy impact test measurements at SCK CEN Belgian Nuclear Research Centre were compared with the nondestructively measured magnetic parameters. A definite correlation was found between magnetic descriptors and the ductile-to-brittle transition temperature (DBTT), regardless of the type of material or irradiation condition. The results suggest that this “calibration curve“ can be used to estimate the DBTT from non-destructive measurements.

Copyright of Magyar Nőorvosok Lapja is the property of Hungarian Society of Obsterics & Gynaecology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Forward genetic screens link genome modifications to phenotypes, and have been successfully employed to identify oncogenes, tumor suppressor genes and genes involved in metastasis or therapy resistance. In particular, transposon-based insertional mutagenesis screens and CRISPR-based screens are versatile and easy-to-use tools employed in recent years to discover and identify novel cancer-related mechanisms. In this review, we present the contribution of forward genetic screens to our understanding of how EMT is regulated and how it is involved in various aspects of cancer. Epithelial–mesenchymal transition (EMT) is a process of cellular plasticity regulated by complex signaling networks. Under physiological conditions, it plays an important role in wound healing and organ repair. Its importance for human disease is given by its central role in chronic fibroproliferative diseases and cancer, which represent leading causes of death worldwide. In tumors, EMT is involved in primary tumor growth, metastasis and therapy resistance. It is therefore a major requisite to investigate and understand the role of EMT and the mechanisms leading to EMT in order to tackle these diseases therapeutically. Forward genetic screens link genome modifications to phenotypes, and have been successfully employed to identify oncogenes, tumor suppressor genes and genes involved in metastasis or therapy resistance. In particular, transposon-based insertional mutagenesis screens and CRISPR-based screens are versatile and easy-to-use tools applied in recent years to discover and identify novel cancer-related mechanisms. Here, we review the contribution of forward genetic screens to our understanding of how EMT is regulated and how it is involved in various aspects of cancer. Based on the current literature, we propose these methods as additional tools to investigate EMT. [ABSTRACT FROM AUTHOR]

The influence of neutron irradiation degradation on reactor pressure vessel steel was investigated. Large blocks were irradiated by neutrons in the BR2 reactor at a low irradiation temperature. They were measured by a nondestructive magnetic method, magnetic adaptive testing, before and after the neutron irradiation. It was shown that the modification of the magnetic parameters due to the neutron irradiation was well detectable by this nondestructive method. It was also shown that the influence of neutron irradiation could be detected with a reasonable signal-to-noise ratio through the cladding. The present results are considered as a first step towards the application of magnetic adaptive testing in the nuclear industry. [ABSTRACT FROM AUTHOR]

This paper presents the names adopted by monks of the (canonical) Premonstratensian Order at Jászóvár during the 19th century, after the 1802 restitution of the Order. It gives a brief introduction to the history of the Premonstratensianian Provostship at Jászóvár, and discusses events that happened before the abolition and after the restitution of the monastery. The paper lists the names adopted by the monks; shows the characteristics of the naming/name-choosing processes, focusing on motivational factors; and classifies the monastic names by their origins and by their semantic features. The study highlights the importance of choosing monastic names after the founder and the saints of the Order.

A novel nondestructive method called magnetic adaptive testing has been previously applied to detect the neutron-irradiation-generated structural changes in reactor pressure vessel steel material. This method has been found to be a useful tool for this purpose, and good correlation—as a tendency—has been found between the estimated ductile-to-brittle transition temperature and magnetic parameters. However, a significant scattering of measured points was also observed for the investigated set of Charpy specimens. The main result of the work was that by magnetic selection of samples, the scatter can be notably reduced. As a conclusion, the magnetically measured parameters seemed to be precise and reliable for the detection of embrittlement of the reactor pressure vessel steel, with lower scattering of points than in the conventionally used destructive mechanical characteristics (ductile-to-brittle transition temperature). This result is surprising and needs further verification. The purpose of the present work is to repeat the measurement on irradiated reactor steel blocks. In this work, instead of the DBTT transition temperature, individually measured Vickers hardness (VH) data were used to help characterize the mechanical properties of the material. The so-called "property transformation" is a known and applied technique in the nuclear industry. The mechanical property characterized by the transition temperature cannot be determined individually for each specimen; instead, it can be obtained only on a set of samples by statistical fitting. Therefore, the individually measured Vickers hardness values can be utilized in order to predict the individual transition temperature values by the help of the property transformation technique. In this paper, however, not these derived transition temperature values, but their origins, the Vickers hardness values, are studied in a direct manner. The same behavior of blocks was observed as in the case of Charpy specimens, which is considered to validate the previously published results. As a possible reason for the scattering of points, large magnetic inhomogeneity of samples cut even from the same block was also proved. The magnetic parameters and Vickers hardness correlate well with each other. This result justifies the potential future application of magnetic techniques in practice aimed at the regular inspection of nuclear reactors. [ABSTRACT FROM AUTHOR]

Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in transendothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-β-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-β-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation.

Monastic names in the Premonstratensian Order at Jászóvár in the century following the 1802 restitution of the Order This paper presents the names adopted by monks of the (canonical) Premonstratensian Order at Jászóvár during the 19th century, after the 1802 restitution of the Order. It gives a brief introduction to the history of the Premonstratensianian Provostship at Jászóvár, and discusses events that happened before the abolition and after the restitution of the monastery. The paper lists the names adopted by the monks; shows the characteristics of the naming/name-choosing processes, focusing on motivational factors; and classifies the monastic names by their origins and by their semantic features. The study highlights the importance of choosing monastic names after the founder and the saints of the Order.

Transient eddy current analysis of pulsed eddy current testing was performed by time-stepping method and Fourier transform method. The characteristics of two methods were evaluated by using a simple model. The accuracy was examined by the comparison of calculated and measured data. The calculated results of the two methods provided good agreement with measured data. However, it was clear that the Fourier transform method provided higher accuracy of amplitude than the time-stepping method. As a three-dimensional problem of pulsed eddy current testing, the TEAM Workshop Problem 27 was analyzed by an edge-element finite element method. Index Terms--Eddy current analysis, eddy current testing, finite element method (FEM).