bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlated Response to Selection for Litter Size Residual Variability in Rabbits’ Body Condition
Authors: Agea Iván , García María de la Luz , Blasco Agustín , Massányi Peter , Capcarová Marcela , Argente María-José
Published: December 2020

A divergent selection experiment for residual variance of litter size at birth was carried out in rabbits during twelve generations. Residual variance of litter size was estimated as the within-doe variance of litter size after pre-correction for year and season as well as parity and lactation status effects. The aim of this work was to study the correlated response to selection for litter size residual variability in body condition from mating to weaning. Body condition is related directly to an animal’s fat deposits. Perirenal fat is the main fat deposit in rabbits. Individual body weight (IBW) and perirenal fat thickness (PFT) were used to measure body condition at second mating, delivery, 10 days after delivery, and weaning. Litter size of the first three parities was analyzed. Both lines decreased body condition between mating to delivery; however, the decrease in body condition at delivery was lower in the low line, despite this line having higher litter size at birth (+0.54 kits, p = 0.93). The increment of body condition between delivery and early lactation was slightly higher in the low line. On the other hand, body condition affected success of females’ receptivity and fertility at the third mating, e.g., receptive females showed a higher IBW and PFT than unreceptive ones (+129 g and +0.28 mm, respectively), and fertile females had a higher IBW and PFT than unfertile ones (+82 g and +0.28 mm, respectively). In conclusion, the does selected for reducing litter size variability showed a better deal with situations of high-energy demand, such as delivery and lactation, than those selected for increasing litter size variability, which would agree with the better health and welfare condition in the low line.
The Effect of the Type of Non-Caged Housing System, Genotype and Age on the Behaviour of Laying Hens
Authors: Sokołowicz Zofia , Dykiel Magdalena , Topczewska Jadwiga , Krawczyk Józefa , Augustyńska-Prejsnar Anna
Published: December 2020

This study investigated the welfare of laying hens in different non-caged housing systems, namely a deep-litter barn system (BS), a free-range system (FRS) and an organic system (OS). The study was conducted on 270 hens of a native breed Green-legged Partridge (Z-11) and 270 Hy-Line Brown hybrids. Visual scans were performed to record behaviour of hens. Hens were housed in groups of 30 and observed over the course of one day at 20, 36 and 56 weeks of age. Dustbathing, scratching, wing stretching, wing flapping and preening were recorded as comfort behaviours. Pecking, fighting, threatening and chasing were recorded as agonistic behaviours. The percentage of run use was higher in native hens than in commercial hens (p < 0.05). The proportion of hens exhibiting comfort behaviours housed in the FRS and OS was similar but over twice as high as in the BS (p < 0.05). In the FRS and OS, the percentage of hens displaying comfort behaviours increased with age (p < 0.05). In all the production systems, the percentage of birds displaying comfort behaviours was higher in native breed hens than in commercial breeds (p < 0.05). In the BS, the higher proportion of hens displaying an agonistic behaviour was seen more in commercial breed than in the native breed hens (p < 0.05). The percentage of birds displaying an agonistic behaviour declined with hen age, both in commercial and native breed hens.
Validation of the American English Acute Cystitis Symptom Score
Authors: Alidjanov Jakhongir F. , Naber Kurt G. , Pilatz Adrian , Wagenlehner Florian M.
Published: December 2020

The diagnosis of acute uncomplicated cystitis (UC) is usually based on clinical symptoms. The study aims to develop and validate the American-English Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for diagnosis and patient-reported outcome in women with acute uncomplicated cystitis (UC). After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed embedded in a US phase-II trial. 167 female patients with typical symptoms of UC were included in the study following US Food and Drug Administration (FDA) guidance. At Day 1 (diagnosis), the mean (SD) sum score of the six ACSS typical symptoms reached 10.60 (2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favored ACSS criteria (sum score of typical symptoms 0.98 (1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. The American-English ACSS showed high predictive ability and responsiveness and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice, or for self-diagnosis of women with symptoms of UC.
Theoretical Analysis of Fractional Viscoelastic Flow in Circular Pipes: General Solutions
Authors: Gritsenko Dmitry , Paoli Roberto
Published: December 2020

Fractional calculus is a relatively old yet emerging field of mathematics with the widest range of engineering and biomedical applications. Despite being an incredibly powerful tool, it, however, requires promotion in the engineering community. Rheology is undoubtedly one of the fields where fractional calculus has become an integral part of cutting-edge research. There exists extensive literature on the theoretical, experimental, and numerical treatment of various fractional viscoelastic flows in constraint geometries. However, the general theoretical approach that unites several most commonly used models is missing. Here we present exact analytical solutions for fractional viscoelastic flow in a circular pipe. We find velocity profiles and shear stresses for fractional Maxwell, Kelvin–Voigt, Zener, Poynting–Thomson, and Burgers models. The dynamics of these quantities are studied with respect to normalized pipe radius, fractional orders, and elastic moduli ratio. Three different types of behavior are identified: monotonic increase, resonant, and aperiodic oscillations. The models developed are applicable in the widest material range and allow for the alteration of the balance between viscous and elastic properties of the materials.
Mitigating the Impact of Noise on Nonlinear Frequency Division Multiplexing
Authors: Civelli Stella , Forestieri Enrico , Secondini Marco
Published: December 2020

In the past years, nonlinear frequency division multiplexing (NFDM) has been investigated as a potentially revolutionary technique for nonlinear optical fiber communication. However, while NFDM is able to exploit the Kerr nonlinearity, its performance lags behind that of conventional systems. In this work, we first highlight that current implementations of NFDM are strongly suboptimal, and, consequently, oversensitive to noise: the modulation does not ensure a large minimum distance between waveforms, while the detection is not tailored to the statistics of noise. Next, we discuss improved detections strategies and modulation techniques, proposing some effective approaches able to improve NFDM. Different flavors of NFDM are compared through simulations, showing that (i) the NFDM performance can be significantly improved by employing more effective detection strategies, with a 5.6 dB gain in Q-factor obtained with the best strategy compared to the standard strategy; (ii) an additional gain of 2.7 dB is obtained by means of a simple power-tilt modulation strategy, bringing the total gain with respect to standard NFDM to 8.3 dB; and (iii) under some parameters range (rate efficiency η≤30%), the combination of improved modulation and detection allows NFDM to outperform conventional systems using electronic dispersion compensation.
Effect of Thermo-Mechanical Processing on the Corrosion Behavior of Fe−30Mn−5Al−0.5C TWIP Steel
Authors: Martin Ulises , Ress Jacob , Bosch Juan , Bastidas David M.
Published: December 2020

Electrochemical corrosion of thermo-mechanically processed (TMP) and recrystallized Fe−30Mn−5Al−0.5C twinning-induced plasticity (TWIP) steels containing 30 wt.% Mn was studied in a 1.0 wt.% NaCl electrolyte solution. The alkaline nature of the corrosion products containing manganese oxide (MnO) increases the dissolution kinetics of the TWIP steel in acid media, obtaining Mn2+ cations in solution, and producing the hydrogen evolution reaction (HER). X-ray photoelectron spectroscopy (XPS) surface analysis revealed an increased Al2O3 content of 91% in the passive layer of the recrystallized TWIP steel specimen, while in contrast only a 43% Al2O3 was found on the TMP specimen. Additionally, the chemical composition of the surface oxide layer as well as the TWIP alloy microstructure was analyzed by optical microscopy (OM) and scanning electron microscopy (SEM). The results indicate an enhanced corrosion attack for the TMP high-Mn TWIP steel.
Interferometric Measurement of TGF-β Induced Epithelial-Mesenchymal Transition of Tumor Cells
Authors: Varol Rahmetullah , Esmer Gokhan Bora , Uvet Huseyin
Published: December 2020

A three-dimensional profile reconstruction of live cells in dynamic cell cultures is a challenging problem due to the highly scattering nature of cell mediums. Furthermore, it is an interesting problem since these cultures present the optimal in vitro conditions that most closely resemble the cells’ natural conditions. In this paper, we report a holographic method used for imaging during the process of treatment of dynamic cell cultures with transforming growth factor beta (TGF-β) and the subsequent epithelial-mesenchymal transition (EMT). The imaging of dynamic cell cultures presents many challenges for holographic techniques due to the highly scattering and high speed nature of the environment. Here we report the algorithmic workflow we used for decreasing the imaging noise due to the presence of cell medium and achieving high speed reconstruction rates in real time. We also report the prominent morphological features we extracted from the obtained depth maps throughout the experiment. We conducted experiments on four different cell lines: ONCO-DG1, HCT-116, MDA-MB-231, and HUVEC. We observed the EMT process throughout a 48 h period after treatment with TGF-β with 6 h intervals for each sample. We show some examples of the reconstructed depth maps of tumor cells during the EMT phase. From these depth maps we extract some morphological parameters and report how they change after the EMT process is completed. The obtained results indicate that the proposed method presents certain advantages from an optical perspective particularly for applications where a dynamical medium is present. These advantages are lower signal-to-noise ratio (SNR) values and a simple setup compared to the setups used in similar studies. Future studies on this application could lead to the development of a model for the EMT process and its effects on cell to cell interactions.
Pedestrian and Multi-Class Vehicle Classification in Radar Systems Using Rulex Software on the Raspberry Pi
Authors: Daher Ali Walid , Rizik Ali , Randazzo Andrea , Tavanti Emanuele , Chible Hussein , Muselli Marco , Caviglia Daniele D.
Published: December 2020

Nowadays, cities can be perceived as increasingly dangerous places. Usually, CCTV is one of the main technologies used in a modern security system. However, poor light situations or bad weather conditions (rain, fog, etc.) limit the detection capabilities of image-based systems. Microwave radar detection systems can be an answer to this limitation and take advantage of the results obtained by low-cost technologies for the automotive market. Transportation by car may be dangerous, and every year car accidents lead to the fatalities of many individuals. Humans require automated assistance when driving through detecting and correctly classifying approaching vehicles and, more importantly, pedestrians. In this paper, we present the application of machine learning to data collected by a 24 GHz short-range radar for urban classification. The training and testing take place on a Raspberry Pi as an edge computing node operating in a client/server arrangement. The software of choice is Rulex, a high-performance machine learning package controlled through a remote interface. Forecasts with a varying number of classes were performed with one, two, or three classes for vehicles and one for humans. Furthermore, we applied a single forecast for all four classes, as well as cascading forecasts in a tree-like structure while varying algorithms, cascading the block order, setting class weights, and varying the data splitting ratio for each forecast to improve prediction accuracy. In the experiments carried out for the validation of the presented approach, an accuracy of up to 100% for human classification and 96.67% for vehicles, in general, was obtained. Vehicle sub-classes were predicted with 90.63% accuracy for motorcycles and 77.34% accuracy for both cars and trucks.
Comparison of Fiber-to-Waveguide Couplers in Point Diffraction Interferometer Based on Waveguide Reference Wavefront Source
Authors: Chen Yuankai , Bai Jian , Wang Chen , Xue Yingze , Yang Yongying
Published: December 2020

To improve the power of reference wavefront generated by reference wavefront source (RWS) based on silicon nitride (SiN) waveguide in point diffraction interferometer (PDI), we design the Y-branch coupler and grating coupler, and then compare the maximum coupling efficiency, 3 dB fabrication tolerance, 3 dB alignment tolerance and polarization dependent loss of two couplers. Our results show that grating coupler has higher coupling efficiency, lower etching difficulty and alignment difficulty, while Y-branch coupler has lower coating difficulty. To get the maximum efficiency, mode in the fiber must be TE mode no matter for grating coupler or Y-branch coupler. This paper improves the power of the wavefront by selecting appropriate fiber-to-waveguide couplers for waveguide RWS. PDI based on the power improved waveguide RWS is expected to be used in many measurement fields.
Characterization of Responsive Plasters for Passive Moisture and Temperature Control
Authors: Fořt Jan , Kočí Jan , Pokorný Jaroslav , Podolka Luboš , Kraus Michal , Černý Robert
Published: December 2020

Ambient comfort maintenance accompanied by excessive energy consumption is hugely criticized concerning the limited sustainability of the building sector in the long-term. In this sense, the energy reduction strategies based on the employment of passive air-control techniques are viewed as a prospective solution for improved energy performance. In order to contribute to this significant issue, this paper is aimed at the design and material characterization of novel plaster with an improved thermal and humidity control performance. For this purpose, a form-stable diatomite/dodecanol-based phase change material together with superabsorbent polymer are used as admixtures for the passive moderation of indoor air quality by newly designed modified plasters. The experimental assessment of the functional properties by means of mechanical strength, thermal conductivity, and hygric properties is performed. Considering the goal of the paper, particular attention is paid to the characterization of water vapor storage and moisture buffering according to the Nordtest method. Differential scanning calorimetry is employed for the description of phase change intervals as well as the specific enthalpy of phase change. The obtained results point to significant improvements in the hygroscopic performance and increased thermal energy storage that can be used for passive moderation of the indoor temperature and reduction of the relative humidity swings.
Image Reconstruction in Diffuse Optical Tomography Using Adaptive Moment Gradient Based Optimizers: A Statistical Study
Authors: Chakhim Nada , Louzar Mohamed , Lamnii Abdellah , Alaoui Mohammed
Published: December 2020

Diffuse optical tomography (DOT) is an emerging modality that reconstructs the optical properties in a highly scattering medium from measured boundary data. One way to solve DOT and recover the quantities of interest is by an inverse problem approach, which requires the choice of an optimization algorithm for the iterative approximation of the solution. However, the well-established and proven fact of the no free lunch principle holds in general. This paper aims to compare the behavior of three gradient descent-based optimizers on solving the DOT inverse problem by running randomized simulation and analyzing the generated data in order to shade light on any significant difference—if existing at all—in performance among these optimizers in our specific context of DOT. The major practical problems when selecting or using an optimization algorithm in a production context for a DOT system is to be confident that the algorithm will have a high convergence rate to the true solution, reasonably fast speed and high quality of the reconstructed image in terms of good localization of the inclusions and good agreement with the true image. In this work, we harnessed carefully designed randomized simulations to tackle the practical problem of choosing the right optimizer with the right parameters in the context of practical DOT applications, and derived statistical results concerning rate of convergence, speed, and quality of image reconstruction. The statistical analysis performed on the generated data and the main results for convergence rate, reconstruction speed, and quality between three optimization algorithms are presented in the paper at hand.
On Combining Static, Dynamic and Interactive Analysis Security Testing Tools to Improve OWASP Top Ten Security Vulnerability Detection in Web Applications
Authors: Mateo Tudela Francesc , Bermejo Higuera Juan-Ramón , Bermejo Higuera Javier , Sicilia Montalvo Juan-Antonio , Argyros Michael I.
Published: December 2020

The design of the techniques and algorithms used by the static, dynamic and interactive security testing tools differ. Therefore, each tool detects to a greater or lesser extent each type of vulnerability for which they are designed for. In addition, their different designs mean that they have different percentages of false positives. In order to take advantage of the possible synergies that different analysis tools types may have, this paper combines several static, dynamic and interactive analysis security testing tools—static white box security analysis (SAST), dynamic black box security analysis (DAST) and interactive white box security analysis (IAST), respectively. The aim is to investigate how to improve the effectiveness of security vulnerability detection while reducing the number of false positives. Specifically, two static, two dynamic and two interactive security analysis tools will be combined to study their behavior using a specific benchmark for OWASP Top Ten security vulnerabilities and taking into account various scenarios of different criticality in terms of the applications analyzed. Finally, this study analyzes and discuss the values of the selected metrics applied to the results for each n-tools combination.
On Ad Hoc Communication in Industrial Environments
Authors: Sauer Christian , Schmidt Marco , Lyczkowski Eike
Published: December 2020

Wireless communication is becoming vital in the industrial environment. New communication technologies, including ad hoc communication, are researched for this application. A thorough understanding regarding the connection characteristics of industrial networks could benefit this trend. In this work it was possible to record the time-variant network topology of such a network utilizing a novel method. Using this method and the generated recordings, novel insights into the behavior of industrial ad hoc networks are presented. The recorded time-variant topology, the tools and method of acquisition, and tools for processing and examination are published. This enables researchers and engineers to check their communication technologies in terms of applicability to the industrial use case and record more network topologies in a wide variety of wireless networking scenarios.
A Large-Deformation Gradient Damage Model for Single Crystals Based on Microdamage Theory
Authors: Aslan Ozgur , Bayraktar Emin
Published: December 2020

This work aims at the unification of the thermodynamically consistent representation of the micromorphic theory and the microdamage approach for the purpose of modeling crack growth and damage regularization in crystalline solids. In contrast to the thermodynamical representation of the microdamage theory, micromorphic contribution to flow resistance is defined in a dual fashion as energetic and dissipative in character, in order to bring certain clarity and consistency to the modeling aspects. The approach is further extended for large deformations and numerically implemented in a commercial finite element software. Specific numerical model problems are presented in order to demonstrate the ability of the approach to regularize anisotropic damage fields for large deformations and eliminate mesh dependency.
Graz Lagrangian Model (GRAL) for Pollutants Tracking and Estimating Sources Partial Contributions to Atmospheric Pollution in Highly Urbanized Areas
Authors: Romanov Aleksey A. , Gusev Boris A. , Leonenko Egor V. , Tamarovskaya Anastasia N. , Vasiliev Alexander S. , Zaytcev Nikolai E. , Philippov Ilia K.
Published: December 2020

Computational modeling allows studying the air quality problems in depth and provides the best solution reducing the population risks. This research demonstrates the Graz Lagrangian model effectiveness for assessing emission sources contributions to the air pollution: particles tracking and accumulation estimate. The article describes model setting up parameters and datasets preparation for the analysis. The experiment simulated the dispersion from the main groups of emission sources for real weather conditions during 96 h of December 2018, when significant excess of NO2, CO, SO2, PM10, and benzo(a)pyrene concentrations were observed in the Krasnoyarsk surface atmospheric layer. The computational domain was a parallelepiped of 40 × 30 × 2.5 km, which was located deep inside the Eurasian continent on a heterogeneous landscape exaggerated by high-rise buildings, with various pollutions sources and the ice-free Yenisei River. The results demonstrated an excellent applicability of the Lagrange model for hourly tracking of particle trajectories, taking into account the urban landscape. For values <1 MPC (maximum permissible concentration) of peak pollutants concentrations, the coincidences were 93 cases, and for values < 0.1 shares of MPC, there were 36 cases out of the total number of 97. The same was found for the average daily concentration for values <1 MPC—31, and for values <0.1 MPC—5 matches out of 44. Wind speeds COR—65.3%, wind directions COR—68.6%. The Graz Lagrangian model showed the ability to simulate air quality problems in the Krasnoyarsk greater area conditions.
Electrical Stimulation of Adipose-Derived Stem Cells in 3D Nanofibrillar Cellulose Increases Their Osteogenic Potential
Authors: Bicer Mesude , Sheard Jonathan , Iandolo Donata , Boateng Samuel Y. , Cottrell Graeme S. , Widera Darius
Published: December 2020

Due to the ageing population, there is a steadily increasing incidence of osteoporosis and osteoporotic fractures. As conventional pharmacological therapy options for osteoporosis are often associated with severe side effects, bone grafts are still considered the clinical gold standard. However, the availability of viable, autologous bone grafts is limited making alternative cell-based strategies a promising therapeutic alternative. Adipose-derived stem cells (ASCs) are a readily available population of mesenchymal stem/stromal cells (MSCs) that can be isolated within minimally invasive surgery. This ease of availability and their ability to undergo osteogenic differentiation makes ASCs promising candidates for cell-based therapies for bone fractures. Recent studies have suggested that both exposure to electrical fields and cultivation in 3D can positively affect osteogenic potential of MSCs. To elucidate the osteoinductive potential of a combination of these biophysical cues on ASCs, cells were embedded within anionic nanofibrillar cellulose (aNFC) hydrogels and exposed to electrical stimulation (ES) for up to 21 days. ES was applied to ASCs in 2D and 3D at a voltage of 0.1 V/cm with a duration of 0.04 ms, and a frequency of 10 Hz for 30 min per day. Exposure of ASCs to ES in 3D resulted in high alkaline phosphatase (ALP) activity and in an increased mineralisation evidenced by Alizarin Red S staining. Moreover, ES in 3D aNFC led to an increased expression of the osteogenic markers osteopontin and osteocalcin and a rearrangement and alignment of the actin cytoskeleton. Taken together, our data suggest that a combination of ES with 3D cell culture can increase the osteogenic potential of ASCs. Thus, exposure of ASCs to these biophysical cues might improve the clinical outcomes of regenerative therapies in treatment of osteoporotic fractures.
Measurement of Serum Testosterone in Nondiabetic Young Obese Men: Comparison of Direct Immunoassay to Liquid Chromatography-Tandem Mass Spectrometry
Authors: Martínez-Escribano Ana , Maroto-García Julia , Ruiz-Galdón Maximiliano , Barrios-Rodríguez Rocío , Álvarez-Millán Juan J. , Cabezas-Sánchez Pablo , Plaza-Andrades Isaac , Molina-Vega María , Tinahones Francisco J. , Queipo-Ortuño María Isabel , Fernández-García José Carlos
Published: December 2020

Hypoandrogenemia, a frequent finding in men with obesity, is defined by low concentrations of serum testosterone. Although immunoassay (IA) is the most used method for the determination of this steroid in clinical practice, liquid chromatography-mass spectrometry (LC-MS/MS) is considered a more reliable method. In this study, we aimed to compare IA versus LC-MS/MS measurement for the diagnosis of hypoandrogenemia in a cohort of 273 nondiabetic young obese men. Mean total testosterone (TT) levels were 3.20 ± 1.24 ng/mL for IA and 3.78 ± 1.4 ng/mL for LC-MS/MS. 53.7% and 26.3% of patients were classified as presenting hypoandrogenemia with IA and LC-MS/MS, respectively. Considering LC-MS/MS as the reference method, sensitivity and specificity of IA were 91.4% (95% CI 82.3–96.8) and 61.1% (95% CI 54.0–67.8), respectively. IA presented an AUC of 0.879 (95% CI 0.83–0.928). Multivariate regression analysis indicated that sex hormone-binding globulin (SHBG) concentrations (p = 0.002) and insulin resistance (p = 0.008) were factors associated with discrepant IA values. In conclusion, the determination of TT by IA in nondiabetic young men with obesity yields lower concentrations of TT than LC-MS/MS, resulting in an equivocal increased diagnosis of hypoandrogenemia, which could lead to inaccurate diagnosis and unnecessary treatment.
Selecting the Most Effective DBS Contact in Essential Tremor Patients Based on Individual Tractography
Authors: Petry-Schmelzer Jan , Dembek Till , Steffen Julia , Jergas Hannah , Dafsari Haidar , Fink Gereon , Visser-Vandewalle Veerle , Barbe Michael
Published: December 2020

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In all investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (p < 0.001). Our data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.
Relevance and Clinical Significance of Magnetic Resonance Imaging of Neurological Manifestations in COVID-19: A Systematic Review of Case Reports and Case Series
Authors: Chowdhary Anisa , Subedi Roshan , Tandon Medha , Wen Sijin , Patel Jenil , Kataria Saurabh , Peterson Sarah , Gwinn Ronald , Elkhooly Mahmoud , Prasad Apoorv , Nirwan Lalit , Adcock Amelia , Sriwastava Shitiz
Published: December 2020

We performed a systematic literature review of neuroimaging, predominantly focusing on magnetic resonance imaging (MRI) findings associated with neurological manifestations of coronavirus disease-2019 (COVID-19). We screened articles from PubMed, Google Scholar and Scopus, looking for reports that would potentially have neuroimaging findings in patients with COVID-19. Data analysis was performed with patient-based data based on the availability of clinical characteristics and outcomes for each individual patient from the studies. Chi square and Wilcoxon rank-sum tests were used to report COVID-19 severity and outcomes based on neurological imaging indicators and pathophysiology. A total of 171 patients with COVID-19 having neurological complications, from 134 studies, were identified in our review. The most common neuroimaging finding was ischemic stroke (62, 36.2%) cases, followed by CNS inflammatory disorder (44, 25.7%), and hemorrhagic stroke (41, 24.0%). Around 51% of all the fatal COVID-19 cases had an ischemic stroke. Among patients with ischemic stroke, the mean age of those who suffered from COVID-19 infection was 57.5 years (SD = 15.4) whereas it was 50.7 years (SD = 15.1) among those without stroke/other diagnosis. Fatality was more common in patients with ischemic stroke compared to those with other diagnosis (40% vs. 22%, p = 0.011). The most frequently published neuroimaging findings in patients with COVID-19 were ischemic stroke, CNS inflammatory disorder, and hemorrhagic disorder. In those studies, ischemic stroke was associated with fatality, and was more frequently seen in older patients. Based on our findings, early usage of MRI in COVID-19 patients may be recommended.
Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
Authors: Kleppe Andreas , Albregtsen Fritz , Trovik Jone , Kristensen Gunnar B. , Danielsen Håvard E.
Published: December 2020

Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (r ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery.
Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis
Authors: Ussowicz Marek , Mielcarek-Siedziuk Monika , Musiał Jakub , Stachowiak Mateusz , Węcławek-Tompol Jadwiga , Sęga-Pondel Dorota , Frączkiewicz Jowita , Trelińska Joanna , Raciborska Anna
Published: December 2020

Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.
Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer
Authors: Schwarzmueller Laura , Bril Oscar , Vermeulen Louis , Léveillé Nicolas
Published: December 2020

Maintenance of the intestinal epithelium is dependent on the control of stem cell (SC) proliferation and differentiation. The fine regulation of these cellular processes requires a complex dynamic interplay between several signaling pathways, including Wnt, Notch, Hippo, EGF, Ephrin, and BMP/TGF-β. During the initiation and progression of colorectal cancer (CRC), key events, such as oncogenic mutations, influence these signaling pathways, and tilt the homeostatic balance towards proliferation and dedifferentiation. Therapeutic strategies to specifically target these deregulated signaling pathways are of particular interest. However, systemic blocking or activation of these pathways poses major risks for normal stem cell function and tissue homeostasis. Interestingly, long non-coding RNAs (lncRNAs) have recently emerged as potent regulators of key cellular processes often deregulated in cancer. Because of their exceptional tissue and tumor specificity, these regulatory RNAs represent attractive targets for cancer therapy. Here, we discuss how lncRNAs participate in the maintenance of intestinal homeostasis and how they can contribute to the deregulation of each signaling pathway in CRC. Finally, we describe currently available molecular tools to develop lncRNA-targeted cancer therapies.
NAMPT Over-Expression Recapitulates the BRAF Inhibitor Resistant Phenotype Plasticity in Melanoma
Authors: Audrito Valentina , Messana Vincenzo Gianluca , Moiso Enrico , Vitale Nicoletta , Arruga Francesca , Brandimarte Lorenzo , Gaudino Federica , Pellegrino Elisa , Vaisitti Tiziana , Riganti Chiara , Piva Roberto , Deaglio Silvia
Published: December 2020

Serine–threonine protein kinase B-RAF (BRAF)-mutated metastatic melanoma (MM) is a highly aggressive type of skin cancer. Treatment of MM patients using BRAF/MEK inhibitors (BRAFi/MEKi) eventually leads to drug resistance, limiting any clinical benefit. Herein, we demonstrated that the nicotinamide adenine dinucleotide (NAD)-biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) is a driving factor in BRAFi resistance development. Using stable and inducible NAMPT over-expression systems, we showed that forced NAMPT expression in MM BRAF-mutated cell lines led to increased energy production, MAPK activation, colony-formation capacity, and enhance tumorigenicity in vivo. Moreover, NAMPT over-expressing cells switched toward an invasive/mesenchymal phenotype, up-regulating expression of ZEB1 and TWIST, two transcription factors driving the epithelial to mesenchymal transition (EMT) process. Consistently, within the NAMPT-overexpressing cell line variants, we observed an increased percentage of a rare, drug-effluxing stem cell-like side population (SP) of cells, paralleled by up-regulation of ABCC1/MRP1 expression and CD133-positive cells. The direct correlation between NAMPT expression and gene set enrichments involving metastasis, invasiveness and mesenchymal/stemness properties were verified also in melanoma patients by analyzing The Cancer Genome Atlas (TCGA) datasets. On the other hand, CRISPR/Cas9 full knock-out NAMPT BRAFi-resistant MM cells are not viable, while inducible partial silencing drastically reduces tumor growth and aggressiveness. Overall, this work revealed that NAMPT over-expression is both necessary and sufficient to recapitulate the BRAFi-resistant phenotype plasticity.
A Confidence Habitats Methodology in MR Quantitative Diffusion for the Classification of Neuroblastic Tumors
Authors: Cerdá Alberich Leonor , Sangüesa Nebot Cinta , Alberich-Bayarri Angel , Carot Sierra José Miguel , Martínez de las Heras Blanca , Veiga Canuto Diana , Cañete Adela , Martí-Bonmatí Luis
Published: December 2020

Background/Aim: In recent years, the apparent diffusion coefficient (ADC) has been used in many oncology applications as a surrogate marker of tumor cellularity and aggressiveness, although several factors may introduce bias when calculating this coefficient. The goal of this study was to develop a novel methodology (Fit-Cluster-Fit) based on confidence habitats that could be applied to quantitative diffusion-weighted magnetic resonance images (DWIs) to enhance the power of ADC values to discriminate between benign and malignant neuroblastic tumor profiles in children. Methods: Histogram analysis and clustering-based algorithms were applied to DWIs from 33 patients to perform tumor voxel discrimination into two classes. Voxel uncertainties were quantified and incorporated to obtain a more reproducible and meaningful estimate of ADC values within a tumor habitat. Computational experiments were performed by smearing the ADC values in order to obtain confidence maps that help identify and remove noise from low-quality voxels within high-signal clustered regions. The proposed Fit-Cluster-Fit methodology was compared with two other methods: conventional voxel-based and a cluster-based strategy. Results: The cluster-based and Fit-Cluster-Fit models successfully differentiated benign and malignant neuroblastic tumor profiles when using values from the lower ADC habitat. In particular, the best sensitivity (91%) and specificity (89%) of all the combinations and methods explored was achieved by removing uncertainties at a 70% confidence threshold, improving standard voxel-based sensitivity and negative predictive values by 4% and 10%, respectively. Conclusions: The Fit-Cluster-Fit method improves the performance of imaging biomarkers in classifying pediatric solid tumor cancers and it can probably be adapted to dynamic signal evaluation for any tumor.
Rapalink-1 Targets Glioblastoma Stem Cells and Acts Synergistically with Tumor Treating Fields to Reduce Resistance against Temozolomide
Authors: Vargas-Toscano Andres , Nickel Ann-Christin , Li Guanzhang , Kamp Marcel Alexander , Muhammad Sajjad , Leprivier Gabriel , Fritsche Ellen , Barker Roger A. , Sabel Michael , Steiger Hans-Jakob , Zhang Wei , Hänggi Daniel , Kahlert Ulf Dietrich
Published: December 2020

Glioblastoma (GBM) is a lethal disease with limited clinical treatment options available. Recently, a new inhibitor targeting the prominent cancer signaling pathway mTOR was discovered (Rapalink-1), but its therapeutic potential on stem cell populations of GBM is unknown. We applied a collection of physiological relevant organoid-like stem cell models of GBM and studied the effect of RL1 exposure on various cellular features as well as on the expression of mTOR signaling targets and stem cell molecules. We also undertook combination treatments with this agent and clinical GBM treatments tumor treating fields (TTFields) and the standard-of-care drug temozolomide, TMZ. Low nanomolar (nM) RL1 treatment significantly reduced cell growth, proliferation, migration, and clonogenic potential of our stem cell models. It acted synergistically to reduce cell growth when applied in combination with TMZ and TTFields. We performed an in silico analysis from the molecular data of diverse patient samples to probe for a relationship between the expression of mTOR genes, and mesenchymal markers in different GBM cohorts. We supported the in silico results with correlative protein data retrieved from tumor specimens. Our study further validates mTOR signaling as a druggable target in GBM and supports RL1, representing a promising therapeutic target in brain oncology.
TMEFF2: A Transmembrane Proteoglycan with Multifaceted Actions in Cancer and Disease
Authors: Masood Motasim , Grimm Stefan , El-Bahrawy Mona , Yagüe Ernesto
Published: December 2020

Transmembrane protein with an EGF-like and two Follistatin-like domains 2 (TMEFF2) is a 374-residue long type-I transmembrane proteoglycan which is proteolytically shed from the cell surface. The protein is involved in a range of functions including metabolism, neuroprotection, apoptosis, embryonic development, onco-suppression and endocrine function. TMEFF2 is methylated in numerous cancers, and an inverse correlation with the stage, response to therapy and survival outcome has been observed. Moreover, TMEFF2 methylation increases with breast, colon and gastric cancer progression. TMEFF2 is methylated early during oncogenesis in breast and colorectal cancer, and the detection of methylated free-circulating TMEFF2 DNA has been suggested as a potential diagnostic tool. The TMEFF2 downregulation signature equals and sometimes outperforms the Gleason and pathological scores in prostate cancer. TMEFF2 is downregulated in glioma and cotricotropinomas, and it impairs the production of adrenocorticotropic hormone in glioma cells. Interestingly, through binding the amyloid β protein, its precursor and derivatives, TMEFF2 provides neuroprotection in Alzheimer’s disease. Despite undergoing extensive investigation over the last two decades, the primary literature regarding TMEFF2 is incoherent and offers conflicting information, in particular, the oncogenic vs. onco-suppressive role of TMEFF2 in prostate cancer. For the first time, we have compiled, contextualised and critically analysed the vast body of TMEFF2-related literature and answered the apparent discrepancies regarding its function, tissue expression, intracellular localization and oncogenic vs. onco-suppressive role.
Optimization of Fenton Technology for Recalcitrant Compounds and Bacteria Inactivation
Authors: Salgado Pablo , Frontela José Luis , Vidal Gladys
Published: December 2020

In this work, the Fenton technology was applied to decolorize methylene blue (MB) and to inactivate Escherichia coli K12, used as recalcitrant compound and bacteria models respectively, in order to provide an approach into single and combinative effects of the main process variables influencing the Fenton technology. First, Box–Behnken design (BBD) was applied to evaluate and optimize the individual and interactive effects of three process parameters, namely Fe2+ concentration (6.0 × 10−4, 8.0 × 10−4 and 1.0 × 10−3 mol/L), molar ratio between H2O2 and Fe2+ (1:1, 2:1 and 3:1) and pH (3.0, 4.0 and 5.0) for Fenton technology. The responses studied in these models were the degree of MB decolorization (D%MB), rate constant of MB decolorization (kappMB) and E. coli K12 inactivation in uLog units (IuLogEC). According to the results of analysis of variances all of the proposed models were adequate with a high regression coefficient (R2 from 0.9911 to 0.9994). BBD results suggest that [H2O2]/[Fe2+] values had a significant effect only on D%MB response, [Fe2+] had a significant effect on all the responses, whereas pH had a significant effect on D%MB and IuLogEC. The optimum conditions obtained from response surface methodology for D%MB ([H2O2]/[Fe2+] = 2.9, [Fe2+] = 1.0 × 10−3 mol/L and pH = 3.2), kappMB ([H2O2]/[Fe2+] = 1.7, [Fe2+] = 1.0 × 10−3 mol/L and PH = 3.7) and IuLogEC ([H2O2]/[Fe2+] = 2.9, [Fe2+] = 7.6 × 10−4 mol/L and pH= 3.2) were in good agreement with the values predicted by the model.
Characteristics and Behavior of Different Catalysts Used for Water Decontamination in Photooxidation and Ozonation Processes
Authors: Rivera-Utrilla José , López-Ramón María Victoria , Sánchez-Polo Manuel , Álvarez Miguel Ángel , Velo-Gala Inmaculada
Published: December 2020

The objective of this study was to summarize the results obtained in a wide research project carried out for more than 15 years on the catalytic activity of different catalysts (activated carbon, metal–carbon xerogels/aerogels, iron-doped silica xerogels, ruthenium metal complexes, reduced graphene oxide-metal oxide composites, and zeolites) in the photooxidation (by using UV or solar radiation) and ozonation of water pollutants, including herbicides, naphthalenesulfonic acids, sodium para-chlorobenzoate, nitroimidazoles, tetracyclines, parabens, sulfamethazine, sodium diatrizoate, cytarabine, and surfactants. All catalysts were synthesized and then texturally, chemically, and electronically characterized using numerous experimental techniques, including N2 and CO2 adsorption, mercury porosimetry, thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectroscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, diffuse reflectance UV–vis spectroscopy, photoluminescence analysis, and transmission electron microscopy. The behavior of these materials as photocatalysts and ozonation catalysts was related to their characteristics, and the catalytic mechanisms in these advanced oxidation processes were explored. Investigations were conducted into the effects on pollutant degradation, total organic carbon reduction, and water toxicity of operational variables and the presence of different chemical species in ultrapure, surface, ground, and wastewaters. Finally, a review is provided of the most recent and relevant published studies on photocatalysis and catalyzed ozonation in water treatments using similar catalysts to those examined in our project.