bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutraceutical Profile of “Carosello” (Cucumis melo L.) Grown in an Out-of-Season Cycle under LEDs
Authors: Palmitessa Onofrio Davide , Durante Miriana , Somma Annalisa , Mita Giovanni , D’Imperio Massimiliano , Serio Francesco , Santamaria Pietro
Published: April 2022

The world population is projected to increase to 9.9 billion by 2050 and, to ensure food security and quality, agriculture must sustainably multiply production, increase the nutritional value of fruit and vegetables, and preserve genetic variability. In this work, an Apulian landrace of Cucumis melo L. called “Carosello leccese” was grown in a greenhouse with a soilless technique under light-emitting diodes (LEDs) used as supplementary light system. The obtained results showed that “Carosello leccese” contains up to 71.0 mg·g−1 dried weight (DW) of potassium and several bioactive compounds important for human health such as methyl gallate (35.58 µg·g−1 DW), α-tocopherol (10.12 µg·g−1 DW), and β-carotene (up to 9.29 µg·g−1 DW under LEDs). In fact, methyl gallate has antioxidative and antiviral effects in vitro and in vivo, tocopherols are well recognized for their effective inhibition of lipid oxidation in foods and biological systems and carotenoids are known to be very efficient physical and chemical quenchers of singlet oxygen. Finally, it was demonstrated that the LEDs’ supplementary light did not negatively influence the biochemical profile of the peponids, confirming that it can be considered a valid technique to enhance horticultural production without reducing the content of the bioactive compounds of the fruits.
Examining the Effects of Induced Plant Defenses on Spodoptera frugiperda Performance
Authors: Garvey Michael , Costanza Kale , Grimmell Scott , Elderd Bret D.
Published: April 2022

Knowing the duration insect pests are in the environment is vital for growers to determine management schemes and apply treatments. Unfortunately, experiments to determine long-term insect performance across plant cultivars are infrequently conducted. With that in mind, we report here the performance of Spodoptera frugiperda, the fall armyworm, on jasmonic acid (JA) induced/non-induced soybean cultivars. JA induction increases plant defensive compounds and can be considered an equivalent to a plant’s response to herbivory. S. frugiperda is a global pest, with infestations in soybeans becoming an emerging problem, making information on this pest’s performance on soybeans warranted. Thus, we reared larvae on two different soybean cultivars with contrasting defensive strategies when induced with JA and measured 7-day survival, development time to pupation, and pupal mass. Plant cultivar and JA induction were both important causes of mortality. Although plant cultivars varied in their amounts of constitutive/inducible defenses, this did not cause an interactive effect between plant cultivar and induction. Insect development to pupation was also extended when fed on induced plants regardless of cultivar, while pupal mass was not affected. Overall, induced plant defenses lowered larval survival and extended development time which would alleviate pest pressure and extend the period growers have for detecting infestations.
4D Flow MRI in Ascending Aortic Aneurysms: Reproducibility of Hemodynamic Parameters
Authors: Juffermans Joe F. , van Assen Hans C. , te Kiefte Bastiaan J. C. , Ramaekers Mitch J. F. G. , van der Palen Roel L. F. , van den Boogaard Pieter , Adriaans Bouke P. , Wildberger Joachim E. , Dekkers Ilona A. , Scholte Arthur J. H. A. , Schalla Simon , Lamb Hildo J. , Westenberg Jos J. M.
Published: April 2022

(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 ± 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16–30% and ICC = 0.84–0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3–26% and ICC = 0.87–1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3–10% and ICC = 0.96–1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients.
Mechanism and Algorithm for Stable Trading Matching between Coal Mining and Power Generation Companies in China
Authors: Shi Ruyi , Li Zheng , Tang Zhenpeng , Wang Di
Published: April 2022

This paper is concerned with stable trading between the coal mining and power generation companies in China. Under the current marketized coal and planned electricity price systems, barriers to price shifting between coal and electricity are created and conflicts between the two sectors are aggravated. The stable trading matching between coal mining and power generation companies is not only an effective means to resolve the conflict in the coal trading market, but also a ballast stone for price stabilization and supply guarantees in coal trading. Based on the two-sided matching theory, this paper starts from the micro market preference and matching willingness of coal mining and power generation companies, puts forward the conceptual framework of the pairwise stable matching of both sides, innovates a mechanism for trading between coal mining and power generation companies, and designs a stable trading matching algorithm. The algorithm has certain theoretical innovation significance from the matching problem of non-separable commodities to that of separable commodities considering the trading volume between coal mining and power generation companies. Furthermore, it is a complement and perfection of the existing coal–power trading platform in its transaction mechanism and trading function. The results reveal that the trading relations between coal mining and power generation companies under the stable matching mechanism are resistant to disintegration and that the pairwise stable matching result is sensitive.
An Empirical Assessment of Performance of Data Balancing Techniques in Classification Task
Authors: Jadhav Anil , M. Mostafa Samih M. , Elmannai Hela , Karim Faten Khalid
Published: April 2022

Many real-world classification problems such as fraud detection, intrusion detection, churn prediction, and anomaly detection suffer from the problem of imbalanced datasets. Therefore, in all such classification tasks, we need to balance the imbalanced datasets before building classifiers for prediction purposes. Several data-balancing techniques (DBT) have been discussed in the literature to address this issue. However, not much work is conducted to assess the performance of DBT. Therefore, in this research paper we empirically assess the performance of the data-preprocessing-level data-balancing techniques, namely: Under Sampling (OS), Over Sampling (OS), Hybrid Sampling (HS), Random Over Sampling Examples (ROSE), Synthetic Minority Over Sampling (SMOTE), and Clustering-Based Under Sampling (CBUS) techniques. We have used six different classifiers and twenty-five different datasets, that have varying levels of imbalance ratio (IR), to assess the performance of DBT. The experimental results indicate that DBT helps to improve the performance of the classifiers. However, no significant difference was observed in the performance of the US, OS, HS, SMOTE, and CBUS. It was also observed that performance of DBT was not consistent across varying levels of IR in the dataset and different classifiers.
A Taxonomy for Threat Actors’ Delivery Techniques
Authors: Villalón-Huerta Antonio , Ripoll-Ripoll Ismael , Marco-Gisbert Hector
Published: April 2022

The main contribution of this paper is to provide an accurate taxonomy for delivery techniques, which allows the detection of novel techniques and the identification of appropriate countermeasures. Delivery is a key stage for offensive cyber operations. During delivery, a threat actor tries to gain an initial foothold into the targeted infrastructure. It is the first step of an offensive cyber operation, where the threat actor interacts with its victim in a hostile way; thus, its success is mandatory for the global achievement of the operation. However, delivery techniques are not well structured among the literature, being in many cases a simple list of techniques with which, if one of them is slightly modified by the threat actor, its detection becomes very difficult. This situation hinders the modeling of hostile actors, a fact that makes it difficult to identify countermeasures to detect and neutralize their malicious activities. In this work, we analyze the current delivery techniques’ classification approaches and the problems linked to them. From this analysis, we propose a novel taxonomy that allows the accurate classification of techniques, overcoming the identified problems and allowing both the discovery of new techniques and the detection of gaps in deployed countermeasures. Our proposal significantly reduces the amount of effort needed to identify, analyze, and neutralize hostile activities from advanced threat actors, in particular their initial access stage. It follows a logical structure that can be easy to expand and adapt, and it can be directly used in the industry’s commonly accepted standards, such as MITRE ATT&CK.
SiamCAM: A Real-Time Siamese Network for Object Tracking with Compensating Attention Mechanism
Authors: Huang Kai , Qin Peixuan , Tu Xuji , Leng Lu , Chu Jun
Published: April 2022

The Siamese-based object tracking algorithm regards tracking as a similarity matching problem. It determines the object location according to the response value of the object template to the search template. When there is similar object interference in complex scenes, it is easy to cause tracking drift. We propose a real-time Siamese network object tracking algorithm combined with a compensating attention mechanism to solve this problem. Firstly, the attention mechanism is introduced in the feature extraction module of the template branch and search branch of the Siamese network to improve the feature representation of the network to the object. The attention mechanism of the search branch enhances the feature representation of both the target and the similar backgrounds simultaneously. Therefore, based on the above two-branch attention, we propose a compensated attention model, which introduces the attention selected by the template branch into the search branch, and improves the discriminative ability of the search branch to the object by using the feature attention weighting of the template branch to the object. Experimental results on three popular benchmarks, including OTB2015, VOT2018, and LaSOT, show that the accuracy and robustness of the algorithm in this paper are adequate. It improved occlusion cases, similar object interference, and high-speed motion. The processing speed on GPU reaches 47 fps, which can achieve real-time object tracking.
Dynamic Stability Assessment of High-Speed Railway Bridges Using Numerical Model Updating
Authors: Kim Sung-Wan , Yun Da-Woon , Chang Sung-Jin , Park Dong-Uk , Park Jae-Bong
Published: April 2022

Numerical model updating using the data measured from the actual structure is required in order to minimize the error between the initial numerical model and the actual structure. Field load tests, which are conducted in order to assess the condition and safety of high-speed railway bridges, are generally expensive and restricted by railway control and weather conditions. Therefore, a method for evaluating the performance of high-speed railway bridges using updated numerical models without conducting field load tests is required. In this study, numerical model updating was performed by using the data measured from the ambient vibration test in order to assess the dynamic stability of high-speed railway bridges. In the ambient vibration test, the measurement point roaming method was applied in order to accurately measure high-speed railway bridges using a limited number of sensors. For numerical model updating, the univariate search method was used, and several measured parameters were updated and converted into the properties of the target bridges in the numerical models. The vertical and torsional modes of the updated numerical models differed by less than 5% from those estimated using the data measured from the target bridges. The responses of the updated numerical models were found to be similar to those measured from the high-speed railway bridges in operation. It was also shown that the updated numerical models could be used to assess the dynamic stability of the bridges.
On the Generalized Bilal Distribution: Some Properties and Estimation under Ranked Set Sampling
Authors: Akhter Zuber , Almetwally Ehab M. , Chesneau Christophe
Published: April 2022

The generalized Bilal (GB) distribution can be defined as the distribution of the median of three independent random variables drawn from the Weibull distribution. Its failure rate function can be monotonic (decreasing or increasing) or upside-down bathtub-shaped. In this study, we aim to reveal some important properties of the GB distribution that have not been considered before. The findings are both theoretical and practical. From the theoretical viewpoint, we present explicit expressions for both single and product moments of order statistics from the GB distribution. The L-moments are derived as well. From the practical viewpoint, the parameter estimations are accomplished using the maximum likelihood (ML) method, which is based on two different sampling schemes: simple random sampling (SRS) and ranked set sampling (RSS) schemes. Furthermore, the asymptotic confidence intervals for the SRS and RSS estimators are discussed. For the sake of comparison and illustration, a simulation study and a real data example are presented. Concluding remarks are given at the end.
Various Series Related to the Polylogarithmic Function
Authors: Stojiljković Vuk , Fabiano Nicola , Pantović Mirjana , Radojević Slobodan , Radenović Stojan , Šešum Ćavić Vesna
Published: April 2022

We derive some series related to the polylogarithmic function, and we also give a new proof to the existing series. Our approach is based on using the summation and integral representation methods. We obtain various interesting series as a consequence.
RNA-seq and Mitochondrial DNA Analysis of Adrenal Gland Metastatic Tissue in a Patient with Renal Cell Carcinoma
Authors: Komiyama Tomoyoshi , Kim Hakushi , Tanaka Masayuki , Isaki Sanae , Yokoyama Keiko , Miyajima Akira , Kobayashi Hiroyuki
Published: April 2022

This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 (ND1) gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes.
Magnetic Fluctuations Entrain the Circadian Rhythm of Locomotor Activity in Zebrafish: Can Cryptochrome Be Involved?
Authors: Krylov Viacheslav V. , Izvekov Evgeny I. , Pavlova Vera V. , Pankova Natalia A. , Osipova Elena A.
Published: April 2022

In the 1960s, it was hypothesized that slow magnetic fluctuations could be a secondary zeitgeber for biological circadian rhythms. However, no comprehensive experimental research has been carried out to test the entrainment of free-running circadian rhythms by this zeitgeber. We studied the circadian patterns of the locomotor activity of zebrafish (Danio rerio) under different combinations of light regimes and slow magnetic fluctuations, based on a record of natural geomagnetic variation. A rapid synchronization of activity rhythms to an unusual 24:12 light/dark cycle was found under magnetic fluctuations with a period of 36 h. Under constant illumination, significant locomotor activity rhythms with 26.17 h and 33.07 h periods were registered in zebrafish exposed to magnetic fluctuations of 26.8 h and 33.76 h, respectively. The results reveal the potential of magnetic fluctuations for entrainment of circadian rhythms in zebrafish and genuine prospects to manipulate circadian oscillators via magnetic fields. The putative mechanisms responsible for the entrainment are discussed, including the possible role of cryptochromes.
Anorexia Nervosa Is Associated with a Shift to Pro-Atherogenic Low-Density Lipoprotein Subclasses
Authors: Stadler Julia T. , Lackner Sonja , Mörkl Sabrina , Meier-Allard Nathalie , Scharnagl Hubert , Rani Alankrita , Mangge Harald , Zelzer Sieglinde , Holasek Sandra J. , Marsche Gunther
Published: April 2022

Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5–24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors.
Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients
Authors: Berends Annika M. A. , Bolhuis Mathieu S. , Nolte Ilja M. , Buitenwerf Edward , Links Thera P. , Timmers Henri J. L. M. , Feelders Richard A. , Eekhoff Elisabeth M. W. , Corssmit Eleonora P. M. , Bisschop Peter H. , Haak Harm R. , van Schaik Ron H. N. , el Bouazzaoui Samira , Wilffert Bob , Kerstens Michiel N.
Published: April 2022

Background: Presurgical treatment with an α-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced α-adrenergic receptor mediated vasoconstriction in patients with pheochromocytoma or sympathetic paraganglioma (PPGL). There is, however, a considerable interindividual variation in the dose-response relationship regarding the magnitude of blood pressure reduction or the occurrence of side effects. We hypothesized that genetically determined differences in α-adrenergic receptor activity contribute to this variability in dose-response relationship. Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and α2A, α2B adrenoreceptor (ADRA2A, ADRA2B) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks. Results: The ADRA1B SNP rs10515807 and the ADRA2A SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (p < 0.05) and with a higher occurrence of side effects (rs10515807) (p = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807. Conclusions: This study suggests that genetic variability of α-adrenergic receptor genes might be associated with the clinically observed variation in beneficial and adverse therapeutic drug responses to α-adrenergic receptor blockers. Further studies in larger cohorts are needed to confirm our observations.
Behavior of Corroded Thin-Walled Concrete-Filled Steel Tubular Stub Columns
Authors: Xue Wen , Chen Ju , Xie Fang , Ye Changhu , Liu Chengbin
Published: April 2022

The behavior of two series of corroded thin-walled concrete-filled steel tubes (CFSTs) was investigated in this paper. One series, called the CT series, consists of fourteen CFST specimens corroded by NaCl solution, while the other, called the AT series, consists of six test pieces corroded in the atmosphere. Outer surfaces of corroded steel tubes were scanned using a 3D scanner machine, and a complete surface profile of each specimen was obtained for corrosion evaluation using different methods in this study. Entire test pieces were compressed to failure, and their behaviors under loading were recorded. It is shown that corrosion has a fractal feature, and it has a significant effect on the ductility of specimens. In addition, FEA models of corroded CFST specimens were established based on the 3D scanning profile results using the ABAQUS program and verified against column test results.
Medullary Thyroid Carcinoma Mutational Spectrum Update and Signaling-Type Inference by Transcriptional Profiles: Literature Meta-Analysis and Study of Tumor Samples
Authors: Minna Emanuela , Romeo Paola , Dugo Matteo , De Cecco Loris , Aiello Antonella , Pistore Federico , Carenzo Andrea , Greco Angela , Borrello Maria Grazia
Published: April 2022

Medullary thyroid carcinoma (MTC) is a rare but aggressive tumor. Although RET and RAS genes are recognized drivers in MTC, associated downstream signaling pathways are largely unknown. In this study, we report 17 sporadic MTCs, collected at our institution, comprising patient-matched primary and lymph node metastatic tumors investigated for mutational and transcriptional profiles. As we identified two uncommon RET deletions (D898_E901del and E632_L633del), we also performed a literature review and meta-analysis to assess the occurrence of unconventional alterations in MTC, focusing on next-generation sequencing studies. We found that new gene alterations are emerging, along with the known RET/RAS drivers, involving not only RET by multiple concurrent mutations or deletions but also other previously underestimated cancer-related genes, especially in sporadic MTCs. In our MTC gene profiles, we found transcriptome similarity between patient-matched tissues and expression of immune genes only by a few samples. Furthermore, we defined a gene signature able to stratify samples into two distinct signaling types, termed MEN2B-like and MEN2A-like. We provide an updated overview of the MTC mutational spectrum and describe how transcriptional profiles can be used to define distinct MTC signaling subtypes that appear to be shared by various gene drivers, including the unconventional ones.
Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma
Authors: Kadow Stephanie , Schumacher Fabian , Kramer Melanie , Hessler Gabriele , Scholtysik René , Oubari Sara , Johansson Patricia , Hüttmann Andreas , Reinhardt Hans Christian , Kleuser Burkhard , Zoratti Mario , Mattarei Andrea , Szabò Ildiko , Gulbins Erich , Carpinteiro Alexander
Published: April 2022

Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium channel Kv1.3 in their mitochondria. The mitochondrial Kv1.3 inhibitors PAPTP and PCARBTP are efficient against two tested human multiple myeloma cell lines (L-363 and RPMI-8226) and against ex vivo cultured, patient-derived myeloma cells, while healthy bone marrow cells are spared from toxicity. Cell death after treatment with PAPTP and PCARBTP occurs via the mitochondrial apoptotic pathway. In addition, we identify up-regulation of the multidrug resistance pump MDR-1 as the main potential resistance mechanism. Combination with ABT-199 (venetoclax), an inhibitor of Bcl2, has a synergistic effect, suggesting that mitochondrial Kv1.3 inhibitors could potentially be used as combination partner to venetoclax, even in the treatment of t(11;14) negative multiple myeloma, which represent the major part of cases and are rather resistant to venetoclax alone. We thus identify mitochondrial Kv1.3 channels as druggable targets against multiple myeloma.
Prospective Real-World Gynaecological Cancer Clinical Registry with Associated Biospecimens: A Collaborative Model to Promote Translational Research between GEICO and the Spanish Biobank Network
Authors: López-Guerrero José Antonio , Mendiola Marta , Pérez-Fidalgo José Alejandro , Romero Ignacio , Torres Ana , Recalde Delia , Molina Elena , Gómez-Raposo César , Levin Ana M. , Herrero Ana , Alarcón Jesús , Esteban Carmen , Marquina Gloria , Rubio María Jesús , Guerra Eva , Sánchez-Lorenzo Luisa , Gálvez-Montosa Fernando , de Juan Ana , Churruca Cristina , Gallego Alejandro , González-Martín Antonio
Published: April 2022

Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer.
The Role of Type-2 Conventional Dendritic Cells in the Regulation of Tumor Immunity
Authors: Saito Yasuyuki , Komori Satomi , Kotani Takenori , Murata Yoji , Matozaki Takashi
Published: April 2022

Conventional dendritic cells (cDCs) orchestrate immune responses to cancer and comprise two major subsets: type-1 cDCs (cDC1s) and type-2 cDCs (cDC2s). Compared with cDC1s, which are dedicated to the activation of CD8+ T cells, cDC2s are ontogenically and functionally heterogeneous, with their main function being the presentation of exogenous antigens to CD4+ T cells for the initiation of T helper cell differentiation. cDC1s play an important role in tumor-specific immune responses through cross-presentation of tumor-derived antigens for the priming of CD8+ T cells, whereas little is known of the role of cDC2s in tumor immunity. Recent studies have indicated that human cDC2s can be divided into at least two subsets and have implicated these cells in both anti- and pro-tumoral immune responses. Furthermore, the efficacy of cDC2-based vaccines as well as cDC2-targeted therapeutics has been demonstrated in both mouse models and human patients. Here we summarize current knowledge about the role of cDC2s in tumor immunity and address whether these cells are beneficial in the context of antitumor immune responses.
A Scintillation Proximity Assay for Real-Time Kinetic Analysis of Chemokine–Chemokine Receptor Interactions
Authors: Eberle Stefanie Alexandra , Gustavsson Martin
Published: April 2022

Chemokine receptors are extensively involved in a broad range of physiological and pathological processes, making them attractive drug targets. However, despite considerable efforts, there are very few approved drugs targeting this class of seven transmembrane domain receptors to date. In recent years, the importance of including binding kinetics in drug discovery campaigns was emphasized. Therefore, kinetic insight into chemokine–chemokine receptor interactions could help to address this issue. Moreover, it could additionally deepen our understanding of the selectivity and promiscuity of the chemokine–chemokine receptor network. Here, we describe the application, optimization and validation of a homogenous Scintillation Proximity Assay (SPA) for real-time kinetic profiling of chemokine–chemokine receptor interactions on the example of ACKR3 and CXCL12. The principle of the SPA is the detection of radioligand binding to receptors reconstituted into nanodiscs by scintillation light. No receptor modifications are required. The nanodiscs provide a native-like environment for receptors and allow for full control over bilayer composition and size. The continuous assay format enables the monitoring of binding reactions in real-time, and directly accounts for non-specific binding and potential artefacts. Minor adaptations additionally facilitate the determination of equilibrium binding metrics, making the assay a versatile tool for the study of receptor–ligand interactions.
BARS Influences Neuronal Development by Regulation of Post-Golgi Trafficking
Authors: Gastaldi Laura , Martín Josefina Inés , Sosa Lucas Javier , Quassollo Gonzalo , Peralta Cuasolo Yael Macarena , Valente Carmen , Luini Alberto , Corda Daniela , Cáceres Alfredo , Bisbal Mariano
Published: April 2022

Neurons are highly polarized cells requiring precise regulation of trafficking and targeting of membrane proteins to generate and maintain different and specialized compartments, such as axons and dendrites. Disruption of the Golgi apparatus (GA) secretory pathway in developing neurons alters axon/dendritic formation. Therefore, detailed knowledge of the mechanisms underlying vesicles exiting from the GA is crucial for understanding neuronal polarity. In this study, we analyzed the role of Brefeldin A-Ribosylated Substrate (CtBP1-S/BARS), a member of the C-terminal-binding protein family, in the regulation of neuronal morphological polarization and the exit of membrane proteins from the Trans Golgi Network. Here, we show that BARS is expressed during neuronal development in vitro and that RNAi suppression of BARS inhibits axonal and dendritic elongation in hippocampal neuronal cultures as well as largely perturbed neuronal migration and multipolar-to-bipolar transition during cortical development in situ. In addition, using plasma membrane (PM) proteins fused to GFP and engineered with reversible aggregation domains, we observed that expression of fission dominant-negative BARS delays the exit of dendritic and axonal membrane protein-containing carriers from the GA. Taken together, these data provide the first set of evidence suggesting a role for BARS in neuronal development by regulating post-Golgi membrane trafficking.
Neutrophil Functional Heterogeneity and Implications for Viral Infections and Treatments
Authors: Chan Lily , Morovati Solmaz , Karimi Negar , Alizadeh Kasra , Vanderkamp Sierra , Kakish Julia E. , Bridle Byram W. , Karimi Khalil
Published: April 2022

Evidence suggests that neutrophils exert specialized effector functions during infection and inflammation, and that these cells can affect the duration, severity, and outcome of the infection. These functions are related to variations in phenotypes that have implications in immunoregulation during viral infections. Although the complexity of the heterogeneity of neutrophils is still in the process of being uncovered, evidence indicates that they display phenotypes and functions that can assist in viral clearance or augment and amplify the immunopathology of viruses. Therefore, deciphering and understanding neutrophil subsets and their polarization in viral infections is of importance. In this review, the different phenotypes of neutrophils and the roles they play in viral infections are discussed. We also examine the possible ways to target neutrophil subsets during viral infections as potential anti-viral treatments.
Store-Operated Calcium Entry and Its Implications in Cancer Stem Cells
Authors: Jardin Isaac , Lopez Jose J. , Sanchez-Collado Jose , Gomez Luis J. , Salido Gines M. , Rosado Juan A.
Published: April 2022

Tumors are composed by a heterogeneous population of cells. Among them, a sub-population of cells, termed cancer stem cells, exhibit stemness features, such as self-renewal capabilities, disposition to differentiate to a more proliferative state, and chemotherapy resistance, processes that are all mediated by Ca2+. Ca2+ homeostasis is vital for several physiological processes, and alterations in the patterns of expressions of the proteins and molecules that modulate it have recently become a cancer hallmark. Store-operated Ca2+ entry is a major mechanism for Ca2+ entry from the extracellular medium in non-excitable cells that leads to increases in the cytosolic Ca2+ concentration required for several processes, including cancer stem cell properties. Here, we focus on the participation of STIM, Orai, and TRPC proteins, the store-operated Ca2+ entry key components, in cancer stem cell biology and tumorigenesis.
Becoming the Metalinguistic Mind: The Development of Metalinguistic Abilities in Children from 5 to 7
Authors: Melogno Sergio , Pinto Maria , Lauriola Marco
Published: April 2022

The object of this study is the development of metalinguistic abilities in an age range—5 to 7 years—where an important turn takes place in education, namely the transition between kindergarten and primary school. Based on the literature starting from the 70’s of the last century, embryonic forms of awareness of how language variation can be manipulated to convey variation in meaning are widely attested in preschoolers. These forms, however, denote an intuitive and implicit level of awareness and will attain a “meta-level”, based on more systematic and explicit reflectiveness, later in development in correlation with cognitive, linguistic, and educational factors. To measure the development of these abilities across the above age range, we recruited 160 native Italian-speaking children from 5 to 7, with comparable numerosity at each age, gender balance, average socio-cultural background, and no cognitive nor neuropsychological impairment. We used 6 metalinguistic tasks, the Raven’s CPM, a lexical and grammatical ability tests. The results showed a significant increase in all the measures across the span considered and correlations between all the measures. A factor analysis on the metalinguistic tasks showed that a single factor accounted for a large part of the common variance.
Psychosocial Difficulties in Preschool-Age Children with Beckwith–Wiedemann Syndrome: An Exploratory Study
Authors: Butti Niccolò , Castagna Annalisa , Montirosso Rosario
Published: April 2022

Beckwith–Wiedemann syndrome (BWS) is a rare overgrowth disease and is not usually associated with intellectual delay. Living with a chronic illness condition such as BWS, however, might affect emotional-behavioral functioning and psychosocial development. To investigate this issue, parents of 30 children with BWS between 1.5 and 6 years old compiled standardized questionnaires assessing the presence of emotional-behavioral and developmental problems. The group mean scores in each scale of behavioral problems fell within the average range. Nevertheless, 23% of the sample presented scores beyond the risk threshold for social withdrawal. As regards psychomotor development, a lower mean score was reliable in the social domain compared to other developmental scales, and in the gross-motor compared to fine-motor functions. Moreover, scores in the at-risk band were reliable in almost half of the children for social development. Notably, older age was overall associated with higher emotional-behavioral and developmental difficulties, while no other socio-demographic or clinical variables accounted for the scores obtained in the questionnaires. These findings ask for a wider consideration by health and educational professionals of the psychosocial functioning of children with BWS, so as to early detect at-risk conditions and eventually promote adequate interventions.
Placental Ultrasonographical Findings during SARS-CoV-2 Infection
Authors: Sotiriou Sotirios , Samara Athina A. , Tsiamalou Iokasti-Apostolia , Donoudis Christos , Seviloglou Eleni , Skentou Chara , Garas Antonios , Daponte Alexandros
Published: April 2022

Infection with SARS-CoV-2 virus (COVID-19) during pregnancy has been associated with several complications. Increasing evidence suggests that COVID-19 infection leaves tell-tale signs of placental injury. During ultrasound examination and placental evaluation of COVID-19 infected pregnancies, we recorded signs of placental involvement, with findings indicating malperfusion, chorangiosis, deciduitis, and subchorionitis. Early detection of placental damage through the use of specific ultrasound findings could indicate which pregnancies are at increased risk for complications.
Models as Epistemic Artifacts for Scientific Reasoning in Science Education Research
Authors: Rost Marvin , Knuuttila Tarja
Published: April 2022

Models are at the core of scientific reasoning and science education. They are especially crucial in scientific and educational contexts where the primary objects of study are unobservables. While empirical science education researchers apply philosophical arguments in their discussions of models and modeling, we in turn look at exemplary empirical studies through the lense of philosophy of science. The studied cases tend to identify modeling with representation, while simultaneously approaching models as tools. We argue that such a dual approach is inconsistent, and suggest considering models as epistemic artifacts instead. The artifactual approach offers many epistemic benefits. The access to unobservable target systems becomes less mysterious when models are not approached as more or less accurate representations, but rather as tools constructed to answer theoretical and empirical questions. Such a question-oriented approach contributes to a more consistent theoretical understanding of modeling and interpretation of the results of empirical research.
Employability within an Education for Sustainability Framework: The Ocean i3 Case Study
Authors: Zinkunegi-Goitia Olatz , Rekalde-Rodríguez Itziar
Published: April 2022

The Council of the European Union recalls that higher education plays a fundamental role in shaping the future of Europe. Therefore, curricula are required to take into account the competences demanded by the job market so that future workers can effectively undertake their professional activities and form part of an active, responsible, ecological, sustainable, and resilient society. Ocean i3 is a cross-border project with the aim of achieving sustainability in the oceans by training students to become environmentally concerned and responsible professionals. This study explores the perception of students and teachers regarding their participation in Ocean i3 and their understanding of employability. A qualitative methodological approach has been used, based on a case study in which semi-structured interviews have been carried out and the Elevator Pitch presentation technique has been applied. Nine students and four teachers from the University of the Basque Country and the University of Bordeaux have been interviewed. The results highlight the importance of the participants’ first contact with the project, the need to be explicit regarding competences that favour employability during the development of the experience, and the need to increase and reinforce internships at social entities located in the territory. It is concluded that the project should focus more explicitly on the concept of employability to raise students’ awareness of the impact that their current participation in Ocean i3 can have on their professional future and insertion in the workplace.
Modeling and Calibration of Active Thermal-Infrared Visual System for Industrial HMI
Authors: Chen Mengjuan , Tian Simeng , He Fan , Fu Qingqin , Gu Qingyi , Wu Baolin
Published: April 2022

In the industrial application of the human-machine interface (HMI), thermal-infrared cameras can detect objects that are limited by visible-spectrum cameras. It can receive the energy radiated by a target through an infrared detector and obtain the thermal image corresponding to the heat distribution field on the target surface. Because of its special imaging principle, a thermal-infrared camera is not affected by the light source when imaging. Compared to visible-spectrum cameras, thermal imaging cameras can better detect defects with poor contrast but temperature differences or internal defects in products. Therefore, it can be used in many specific industrial inspection applications. However, thermal-infrared imaging has the phenomenon of thermal diffusion, which leads to noisy thermal infrared images and limits its applications in high precision industrial environments. In this paper, we proposed a high precision measurement system for industrial HMI based on thermal-infrared vision. The accurate measurement model of the system was established to deal with the problems caused by imaging noise. The experiments conducted suggest that the proposed model and calibration method is valid for the active thermal-infrared visual system and achieves high precision measurements.
Synthesis and Characterization of Gadolinium-Doped Zirconia as a Potential Electrolyte for Solid Oxide Fuel Cells
Authors: Yilmaz Serdar , Cobaner Senel , Yalaz Emine , Amini Horri Bahman
Published: April 2022

Zirconia-based composites with high thermochemical stability and electrochemical activity are the most promising solid electrolytes for manufacturing solid oxide fuel cells (SOFCs). In the present work, nanocrystalline composite powders of gadolinium-doped zirconia (GDZ: Gd2xZr2(1−x)O4−x) with various doping fractions (0.01 ≤ x ≤ 0.16) were synthesized by the Pechini method and applied for the fabrication of several electrolyte pellets to evaluate their physicochemical properties, sinterability, and conductivity. The X-ray diffraction (XRD) patterns and the thermogravimetry/differential thermal analysis (TGA/DTA) of the synthesized powders confirmed the successful formation of nanocrystalline GDZ in the tetragonal phase with complete substitution of gadolinium phase into the zirconia (ZrO2) lattice. The synthesized gadolinium zirconate powders were then shaped into pellet forms using the tape casting method, followed by sintering at 1300 °C (for 2.5 h). The microstructural analysis of the electrolyte pellets showed suitable grain boundary welding at the surface with an acceptable grain growth at the bulk of the T-phase GDZ samples. The impedance measurements indicated that the T-phase GDZ-8 could provide a comparably higher ionic conductivity (with 7.23 × 10−2 S/cm in the air at 800 °C) than the other dopant fractions. The results of this work can help better understand the characteristics and electrochemical performance of the T-phase gadolinium zirconate as a potential electrolyte for the fabrication of SOFCs.
Applicability Assessment of Viscoelastic Surfactants and Synthetic Polymers as a Base of Hydraulic Fracturing Fluids
Authors: Mihail Silin , Lyubov Magadova , Denis Malkin , Polina Krisanova , Sergei Borodin , Andrey Filatov
Published: April 2022

Hydraulic fracturing (HF) is currently the most widespread and effective method of oil production stimulation. The most commonly used fracturing fluid is crosslinked guar gels. However, when using these systems, problems such as clogging of the pore space, cracking, and proppant packing with the remains of the undestroyed polymer arise. Therefore, the efficiency of the hydraulic fracturing process decreases. In this work, compositions based on viscoelastic surfactants (VES) and synthetic polymers (SP) were considered as alternatives capable of minimizing these disadvantages. Most often, the possibility of using a composition as a fracturing fluid is evaluated using rotational viscometry. However, rotational viscometry is not capable of fully assessing the structural and mechanical properties of fracturing fluid. This leads to a reduced spread of systems based on VES and SP. This paper proposes an integrated approach to assessing the effectiveness of a water-based fracturing fluid. The proposed comprehensive approach includes an assessment of the main characteristics of water-based fracturing fluids, including an analysis of their structural and mechanical properties, which is based on a combination of rotational and oscillatory rheology and a comparative analysis of methods for studying the influence of fluids on the reservoir rock. The use of the developed approach to assess the technological properties of fracturing fluids makes it possible to demonstrate the potential applicability of new, unconventional fracturing fluids such as systems based on VES and SP.