What common biomarkers characterize a triple-negative profile in breast cancer?

Triple-negative breast cancers are not a homogeneous subgroup. There is substantial intra-subgroup diversity in tumor biology, prognosis and treatment sensitivity. Then, these triple-negative phenotype (TNP) groups, having specific features, can be again divided into subclasses based on an added immunohistochemical markers. The challenge in treating TNP breast cancers is that they are not responsive to antiestrogens or trastuzumab secondary to negative receptor status, and as a result have a poor prognosis. Therefore, the presence or absence of supplementary markers could help predict which therapies are best suited for patients based on the pattern that their disease markers show. In this review, we will recapitulate the major supplementary biomarkers related to triple-negative breast cancer, which could give new therapeutic options.

Sequence and structural analyses of NSP4 proteins from human group A rotavirus strains detected in Tunisia.

BACKGROUND: The NSP4 protein of group A rotavirus (RVA) has been recognized as a viral enterotoxin and plays important roles in viral pathogenesis and morphogenesis. Domains involved in structural and functional interactions have been proposed mainly based on the simian SA11 strain. METHODS: NSP4 has been classified into 15 different genotypes (E1-E15), and the aim of this study was to analyze the sequences of 46 RVA strains in order to determine the aminoacid (aa) differences between E1 and E2 genotypes. Another aspect was to characterize the structural and physicochemical properties of these strains. RESULTS: Comparison of deduced aa sequences of the NSP4 protein showed that divergences between NSP4 genotypes E1 and E2 were mostly observed in the VP4-binding, the interspecies variable domain (ISVD) and the double-layered particle (DLP) binding domains. Interestingly, uncommon variations in residues 131 and 138, which are known to be important aa in pathogenesis, were found in one unusual animal derived strain belonging to the E2 genotype. Concerning the structural aspect, no significant differences were noted. CONCLUSION: The presence of punctual aa variations in the NSP4 genotypes may indicate that NSP4 mutates mainly via accumulation of point mutations.

Design solutions for the hodoscope of the magnetic proton recoil neutron spectrometer of the SPARC tokamak.

A new 14 MeV neutron spectrometer utilizing the magnetic proton recoil (MPR) technique is under development for the SPARC tokamak. This instrument measures neutrons by converting them into protons, whose momenta are subsequently analyzed using a series of magnets before detection by an array of scintillators known as the hodoscope. In this work, we explore various solutions for the hodoscope detectors through laboratory tests with radioactive sources and simulations. We present findings on light collection and pulse shape discrimination based on detector types, as well as optimal solutions for photo-detectors studying the differences between SiPM and PMT. Our results also led to the determination of a better optimized design for the hodoscope detectors, consisting of a 0.7 cm width and a 13 cm length EJ276D scintillation rod.

Development of a measuring technique based on JET second D-T campaign (DTE2) experience for assessing fusion power at ITER during D-T operation using the radial gamma-ray spectrometer.

The ITER Radial Gamma-Ray Spectrometer (RGRS) consists of three gamma-ray detectors observing the plasma through three collimated, coplanar, radial lines of sight (LoS). The system was initially designed to monitor the runaway electron emission and the alpha-particle density profile [Nocente et al., Nucl. Fusion 57, 076016 (2017)]. This work presents a novel technique for measuring the fusion power during D-T operation using the RGRS. This method is based on the absolute measurement of the 17 MeV fusion gamma-rays and a semi-analytical computation of their transport from the plasma source to the detectors. This approach was initially developed and tested at JET during the second D-T campaign (DTE2) on a single LoS diagnostic [Dal Molin et al., Phys. Rev. Lett. (submitted) (2024); Rebai et al., Phys. Rev. C (submitted) (2024); and Marcer et al., Nucl. Fusion (unpublished) (2024)]. This work exploits the multiple LoS of the RGRS to create a combined virtual diagnostic whose detected fraction of the total plasma emission is less affected by variations in the plasma emission profile, reducing systematic uncertainties on the estimated total emission, compared to the individual detectors.

Conceptual design of a GEM (gas electron multiplier) based gas Cherenkov detector for measurement of 17 MeV gamma rays from T(D, γ)5He in magnetic confinement fusion plasmas.

The only method for assessing the fusion power throughput of a deuterium-tritium (DT) reactor presently relies on determining the absolute number of 14 MeV neutrons produced in the DT plasma. An independent method, developed and investigated during the recent DT campaign at the Joint European Torus, is based on the absolute counting of 17 MeV gamma rays produced by the competing T(D, γ)5He reaction that features a very weak branching ratio (about 3-6 × 10-6) when compared to the main T(D, n)4He reaction. The state-of-the-art spectrometer used for gamma-ray measurements in magnetic confinement fusion plasmas is LaBr3(Ce) scintillator detectors, although they require significant neutron shielding to extract a relatively weak gamma-ray signal from a much more abundant neutron field. A better approach relies on a gamma-ray detector that is intrinsically insensitive to neutrons. We have advanced the design of a gamma-ray counter based on the Cherenkov effect for gamma-rays whose energy exceeds 11 MeV, optimized to work in the neutron-rich environment of a steady-state, magnetically confined fusion plasma device. The gamma-rays interact with an aluminum window and extract electrons that move into the radiator emitting photons via the Cherenkov effect. Since the Cherenkov light consists of few photons (25 on average) in the far UV band (100-200 nm), a pre-amplifier is required to transport the photons to the neutron-shielded location, which may be a few meters away, where the readout elements of the detector, either a silicon or standard photomultiplier tube, are placed. The present work focuses on the development of a scintillating GEM (Gas Electron Multiplier) based pre-amplifier that acts as a Cherenkov photon pre-amplifier and wavelength shifter. This paper presents the result of a set of Garfield++ simulations developed to find the optimal GEM working parameters. A photon gain of 100 is obtained by biasing a single GEM foil to 1 kV.

[Associated factors and sub-clinical myocardial dysfunction in obese patients with masked hypertension]. / L'hypertension artérielle masquée chez les obèses : facteurs associés et atteinte myocardique infraclinique.

INTRODUCTION: Obesity is a worldwide health problem. Masked hypertension is a relatively recent reported entity with a diagnostic problem. The aim of this study was to determine the clinical and paraclinical characteristics and to identify the predictive factors of masked hypertension in obese patients. METHODS: It is a prospective study including obese patients with normal arterial pressure at office. All of these patients were given ambulatory blood pressure measurement (ABPM) to screen for masked hypertension, laboratory tests and a complete echocardiography study. RESULTS: A total of 50 patients were included. The mean age was 46.52±10.4 years. The mean systolic blood pressure (BP) at office was 120.8±8.8mmHg and the mean diastolic BP was 75±7.3mmHg. The prevalence of masked hypertension in obese adults was 36% with a predominantly non-dipper profile (38%). The study of echocardiographic parameters found dilated left atrium (LA) in 16 patients (32%). The left ventricle (LV) was hypertrophied in 32 patients (64%). The overall LV global longitudinal strain (GLS) was on average -18.85±0.9% and the LA GLS was on average 37.35±4.5%. In our study, metabolic syndrome, low HDL cholesterol, elevated fasting blood glucose, hyperuricemia, LA dilatation, LV hypertrophy, diastolic LV dysfunction and altered myocardial deformities were factors associated with masked hypertension in obese adults. CONCLUSION: It is important to screen for hypertension by ambulatory measurement in at-risk obese patients who present associated cardiovascular risk factors to reduce morbidity and mortality. Echocardiography and speckle tracking analysis could be helpful in detection sub-clinical myocardial deterioration in obese patients with masked hypertension.

Role of neutron attenuators for gamma-ray measurements in deuterium-tritium magnetic confinement plasmas.

The Joint European Torus (JET) is the only tokamak in the world able to operate in Deuterium-Tritium (DT) plasmas. A successful DT experimental campaign, the DTE2, has recently been carried out, providing unique opportunities for studying both physics and technological aspects. In particular, it allowed us to investigate and benchmark the solutions adopted to attenuate the significant 14 MeV neutron flux, needed to enable high-resolution gamma-ray spectroscopy measurements on a tokamak. While in inertial confinement experiments, gamma-rays and neutrons are discriminated through time-of-flight techniques; in magnetic confinement experiments, the neutron attenuators are a key element to allow gamma-ray measurements in order to reestablish the 1 × 105 to 1 background to signal ratio. In this paper, the role of the reference neutron attenuators at JET, based on LiH, has been analyzed and described.

A new dedicated signal processing system for gamma-ray spectrometers in high power deuterium-tritium plasma scenarios in tokamaks.

The most performant deuterium-tritium (DT) plasma discharges realized by the Joint European Torus (JET) tokamak in the recent DT campaign have produced neutron yields on the order of 1018 n/s. At such high neutron yields, gamma-ray spectroscopy measurements with scintillators are challenging as events from the neutron-induced background often dominate over the signal, leading to a significant fraction of pileup events and instability of the photodetector gain along with the consequent degradation of the reconstructed spectrum. Here, we describe the solutions adopted for the tangential lanthanum bromide spectrometer installed at JET. A data acquisition system with free streaming mode digitization capabilities for the entire duration of the discharge has been used to solve dead-time related issues and a data reconstruction code with pileup recovery and photodetector gain drift restoration has been implemented for off-line analysis of the data. This work focuses on the acquired data storage and parsing, with a detailed explanation of the pileup recovery and gain drift restoration algorithms.

A high-resolution neutron spectroscopic camera for the SPARC tokamak based on the Jet European Torus deuterium-tritium experience.

Dedicated nuclear diagnostics have been designed, developed, and built within EUROFUSION enhancement programs in the last ten years for installation at the Joint European Torus and capable of operation in high power Deuterium-Tritium (DT) plasmas. The recent DT Experiment campaign, called DTE2, has been successfully carried out in the second half of 2021 and provides a unique opportunity to evaluate the performance of the new nuclear diagnostics and for an understanding of their behavior in the record high 14 MeV neutron yields (up to 4.7 × 1018 n/s) and total number of neutrons (up to 2 × 1019 n) achieved on a tokamak. In this work, we will focus on the 14 MeV high resolution neutron spectrometers based on artificial diamonds which, for the first time, have extensively been used to measure 14 MeV DT neutron spectra with unprecedented energy resolution (Full Width at Half Maximum of ≈1% at 14 MeV). The work will describe their long-term stability and operation over the DTE2 campaign as well as their performance as neutron spectrometers in terms of achieved energy resolution and high rate capability. This important experience will be used to outline the concept of a spectroscopic neutron camera for the SPARC tokamak. The proposed neutron camera will be the first one to feature the dual capability to measure (i) the 2.5 and 14 MeV neutron emissivity profile via the conventional neutron detectors based on liquid or plastics scintillators and (ii) the 14 MeV neutron spectral emission via the use of high-resolution diamond-based spectrometers. The new opportunities opened by the spectroscopic neutron camera to measure plasma parameters will be discussed.

Priming effect in children with Type 1 Diabetes Mellitus.

Previous studies have evidenced cognitive difficulties across various domains in Type 1 Diabetes Mellitus (T1DM) children, but the implicit memory system has not yet been systematically explored.Taking into account that the interplay between memory and perception may be modulated by the semantic category of the stimuli and their salience, we explored explicit and implicit memory using both object and food stimuli to verify whether for T1DM children there is a feebleness in performing the function of memory as a function of the stimuli used.Eighteen T1DM children and 47 healthy children performed an explicit recognition task in which they were requested to judge whether the presented image had already been shown ("old") or not ("new") and an identification priming task in which they were asked to name new and old pictures presented at nine ascending levels of spatial filtering.Results did not reveal any differences between controls and T1DM children in the explicit memory recognition task, whereas some differences between the two groups were found in the identification priming task. In T1DM children, the priming effect was observed only for food images.The dissociation between implicit and explicit memory observed in children with diabetes seems to be modulated by the category of the stimuli, and these results underscore the relevance of taking into account this variable when exploring cognitive functions.

Sensitivity of N170 and late positive components to social categorization and emotional valence.

Previous experiments have shown that categorization of people into two distinct fictive groups has an impact on cognitive processes. The main objective of the present study was to examine whether this mere categorization improves information processing speed and alters early and late onset ERPs during a social judgment task. In a group membership situation, in-group evaluation enhanced information processing speed and occipito-temporal N170 amplitudes, associated with orthographic processing, compared to out-group evaluation, more so for positive than negative attributes. Moreover, negative adjectives elicited larger N170 amplitudes and faster information processing speed than positive adjectives. In contrast, positive adjectives in a non-membership context enhanced a late positive component in prefrontal regions. These results reflect the existence of a motivational top-down influence due to social categorization in early perceptual stages of word processing. These findings are also in accord with the existence of two distinct systems of evaluation, the first implicating an automatic processing represented in occipito-temporal neocortex and the other a more controlled processing represented in PFC.

Risk genotypes and haplotypes of the GLUT1 gene for type 2 diabetic nephropathy in the Tunisian population.

OBJECTIVE: Diabetic nephropathy (DN) is a long-term complication of both type 1 and type 2 diabetes. Genetic studies on DN have been of little help so far, since several genetic association studies have shown conflicting results. Here we report the findings of a case-control study on five SNPs in the glucose transporter 1 (GLUT1) gene. The study investigated the association of five GLUT1 genotypes and haplotypes with DN. RESEARCH DESIGN AND METHODS: All subjects, 126 DN (cases) and 273 type 2 diabetes (controls), were genotyped using the polymerase chain reaction restriction fragment length polymorphism. RESULTS: The TT and the AA genotypes of the Haell and Enh2 SNP1, increased the risk of DN. The study also identified CGT as the highest risk haplotype (4.4-fold) followed by CAT with an increased risk of DN of 2.6-fold. CONCLUSIONS: The GLUT1 gene confers susceptibility to DN in type 2 diabetes patients in the Tunisian population.

Neutron measurements at the ELISE neutral beam test facility and implications for neutron based diagnostics at SPIDER.

Along the route to the development of a neutral beam injector for ITER, the Padua based Source for Production of Ion of Deuterium Extracted from Rf plasma (SPIDER) and megavolt ITER injector and concept advancement facilities will make use of neutron diagnostics to quantify the homogeneity of the neutral beam profile by measuring the map of the neutron emission from the beam dump with the close-contact neutron emission surface mapping (CNESM) system. Neutrons are here produced from beam-target reactions between the deuterium beam and the deuterons previously adsorbed in the calorimeter. In order to aid the interpretation of the diagnostic data, a dedicated experiment on neutron emission from beam-target reactions with beam parameters approaching those expected at SPIDER has been performed at the Extraction from a Large Ion Source Experiment (ELISE) neutral beam test facility. The time trace of neutron emission has been measured using a calibrated liquid scintillator detector at increasing power densities on the target. Compared to calculations based on the local mixing model, a systematic discrepancy was observed exceeding the statistical accuracy of the measurements and increasing as a linear function of the power density. The data are used to derive an empirical temperature dependent correction for applications to neutron measurements at SPIDER.

Design of gamma-ray spectrometers optimized for fast particle studies at ITER.

A set of gamma ray spectrometers has been designed for ITER within the Radial Gamma Ray Spectrometer (RGRS) project. The aim of this project is designing a system, integrated with the ITER radial neutron camera, which is able to measure the gamma-rays emitted from the plasma with a good energy resolution (about 1.5% at 4.44 MeV) and at high counting rates (in excess of 1 MHz). The RGRS will be able to operate both in the D phase and in the full-power DT phase and will measure gamma rays from (i) reactions between fast ions, such as α particles, and light impurities and (ii) bremsstrahlung emission generated by runaway electron interactions with both plasma bulk and tokamak walls. The RGRS detectors are arranged in nine lines of sights (able to cover a radial region with r < a/3), each featuring a large LaBr3 scintillator crystal. Due to the high neutron flux and magnetic field, several solutions have been adopted to guarantee a good signal to background ratio and MHz counting rate capabilities. The RGRS is capable to combine space and energy distribution measurements of α particles and runaway electrons, which will help the study of the fast particle physics in a burning plasma.

(AC) dinucleotide repeat polymorphism in intron 1 of human EGFR shows ethnic specificities and high evidence for association with breast cancer.

A polymorphic AC repeat in intron 1 of the EGFR gene was genotyped on 352 healthy individuals and 118 women with breast cancer sampled from the Kuwaiti and Tunisian populations. We compared allele frequencies in these populations with published data on various ethnic groups. We found very close similarity between Tunisian and Kuwaiti populations for both allelic and genotypic frequencies and in both control and patient groups. Our analysis revealed clear interethnic differences between populations; in Europeans, allele 16 occurred predominantly, whereas in Tunisia and Kuwait allele 17 was the most frequent and allele 20 predominated in Asians. One hundred twenty-three healthy women, matched with the 118 breast cancer patients, were used as controls to test for associations between AC repeat and cancer risk. Strong evidence for such an association was found for allele 18 when considered alone (chi2=27.04, corrected p=0.0000016, OR=3.94) or with longer alleles (>17 repeats) (chi2=20.21, p=0.0005, OR=2.30). This contrasts with Asian populations where allele 16 was identified as the risk allele, showing allele heterogeneity depending on ethnicity.

First neutron spectroscopy measurements with a pixelated diamond detector at JET.

A prototype Single crystal Diamond Detector (SDD) was installed at the Joint European Torus (JET) in 2013 along an oblique line of sight and demonstrated the possibility to carry out neutron spectroscopy measurements with good energy resolution and detector stability in discharges heated by neutral beam injection and radio-frequency waves. Starting from these positive results, within the Vertical Neutron Spectrometer project of the Joint European Torus, we have developed a pixelated instrument consisting of a matrix of 12 independent SDDs, called the Diamond Vertical Neutron Spectrometer (DVNS), which boosts the detection efficiency of a single SDD by an order of magnitude. In this paper we describe the main features of the DVNS, including the detector design, energy resolution, and data acquisition system for on-line processing. Preliminary spectroscopy measurements of 2.5 MeV neutrons from the present deuterium plasma at JET are finally presented.

Neutron emission spectroscopy of DT plasmas at enhanced energy resolution with diamond detectors.

This work presents measurements done at the Peking University Van de Graaff neutron source of the response of single crystal synthetic diamond (SD) detectors to quasi-monoenergetic neutrons of 14-20 MeV. The results show an energy resolution of 1% for incoming 20 MeV neutrons, which, together with 1% detection efficiency, opens up to new prospects for fast ion physics studies in high performance nuclear fusion devices such as SD neutron spectrometry of deuterium-tritium plasmas heated by neutral beam injection.

Response function of single crystal synthetic diamond detectors to 1-4 MeV neutrons for spectroscopy of D plasmas.

A Single-crystal Diamond (SD) detector prototype was installed at Joint European Torus (JET) in 2013 and the achieved results have shown its spectroscopic capability of measuring 2.5 MeV neutrons from deuterium plasmas. This paper presents measurements of the SD response function to monoenergetic neutrons, which is a key point for the development of a neutron spectrometer based on SDs and compares them with Monte Carlo simulations. The analysis procedure allows for a good reconstruction of the experimental results. The good pulse height energy resolution (equivalent FWHM of 80 keV at 2.5 MeV), gain stability, insensitivity to magnetic field, and compact size make SDs attractive as compact neutron spectrometers of high flux deuterium plasmas, such as for instance those needed for the ITER neutron camera.