bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Doorstep, Rodents in Homesteads and Kitchen Gardens
Authors: Balčiauskas Linas , Balčiauskienė Laima
Published: May 2020

Scarcely investigated in terms of small mammals, kitchen gardens and homesteads form a subset of environments. Using results of snap trapping, we present the first data on small mammal species diversity, gender and age structure, relative abundance, body fitness, and reproduction parameters in these commensal habitats (kitchen gardens, homestead gardens, houses, and outbuildings). We expected that (i) house mice should be the dominant species in buildings, while striped field mice should be dominant in gardens, (ii) body condition should be the highest in buildings, (iii) body condition should increase in the autumn, irrespective of the habitat, and (iv) breeding failures in the form of disrupted pregnancies should be observed. Not all of the predictions were confirmed. From the seven recorded species, gardens and outbuildings were dominated by yellow-necked mice, while bank voles dominated in buildings where food was available. The number of recorded species and diversity index increased during the autumn months. The body condition was highest in rodents that were trapped in gardens. It decreased towards winter, with the exception of the striped field mouse. Breeding disturbances were recorded in all of the most numerous species, comprising 16.7–100% of all observed pregnancies.
New Insights into Bioactive Compounds from the Medicinal Plant Spathodea campanulata P. Beauv. and Their Activity against Helicobacter pylori
Authors: Ngnameko Corinne Raïssa , Marchetti Lucia , Zambelli Barbara , Quotadamo Antonio , Roncarati Davide , Bertelli Davide , Njayou Frederic Nico , Smith Stella I. , Moundipa Paul F. , Costi Maria Paola , Pellati Federica
Published: May 2020

The medicinal plant Spathodea campanulata P. Beauv. (Bignoniaceae) has been traditionally applied for the prevention and treatment of diseases of the kidney and urinary system, the skin, the gastrointestinal tract, and inflammation in general. The present work shows for the first time how chemical components from this plant inhibit Helicobacter pylori growth by urease inhibition and modulation of virulence factors. The crude extract and the main fractions of S. campanulata bark were tested on H. pylori isolated strains and the active ones were further fractionated. Fractions and sub-fractions of the plant crude extract were characterized by ultra-high-performance liquid chromatographic tandem high resolution-mass spectrometry detection (UHPLC-HRMS). Several phenolics and triterpenoids were identified. Among the sub-fractions obtained, SB2 showed the capacity to inhibit H. pylori urease in a heterologous bacterial model. One additional sub-fraction (SE3) was able to simultaneously modulate the expression of two adhesins (HopZ and BabA) and one cytotoxin (CagA). The flavonol kaempferol was identified as the most interesting compound that deserves further investigation as a new hit for its capacity to modulate H. pylori virulence factors.
Soluble Phenolic Composition Tailored by Germination Conditions Accompany Antioxidant and Anti-Inflammatory Properties of Wheat
Authors: Tomé-Sánchez Irene , Martín-Diana Ana Belén , Peñas Elena , Bautista-Expósito Sara , Frias Juana , Rico Daniel , González-Maillo Lorena , Martinez-Villaluenga Cristina
Published: May 2020

Knowledge on the specific variation in the phenolic composition of wheat defined by germination conditions and its relationship with antioxidant and anti-inflammatory properties of sprouts would be useful to improve the functional value of wheat-derived products. Variation in soluble phenolic composition, antioxidant and anti-inflammatory potential of wheat was examined in a range of germination temperature (12–21 °C) and time (1–7 d). Response surface methodology was applied for building lineal and quadratic models to find optimal germination conditions to improve nutraceutical value of wheat sprouts using the desirability (D) function. Phenolics were determined by HPLC-DAD-ESI-MS. In vitro biochemical methods and lipopolysaccharide stimulated RAW264.7 macrophages were used to determine antiradical and anti-inflammatory activities of wheat sprouts. Accumulation of soluble phenolic acids, flavone C-glycosides and lignans in sprouts was positively influenced by germination temperature and time. Increased concentration of individual polyphenols was directly associated with improved ability of sprouts for radical scavenging and reduction of tumor necrosis factor α and interleukin 6 in macrophages. Optimal desirability (D = 0.89) for improved nutraceutical value of wheat sprouts was achieved at 21 °C for 7 d. This information would be useful for food industry aiming at producing wheat-based products with better nutritional and healthy properties.
The Structural Integrity of the Model Lipid Membrane during Induced Lipid Peroxidation: The Role of Flavonols in the Inhibition of Lipid Peroxidation
Authors: Sadžak Anja , Mravljak Janez , Maltar-Strmečki Nadica , Arsov Zoran , Baranović Goran , Erceg Ina , Kriechbaum Manfred , Strasser Vida , Přibyl Jan , Šegota Suzana
Published: May 2020

The structural integrity, elasticity, and fluidity of lipid membranes are critical for cellular activities such as communication between cells, exocytosis, and endocytosis. Unsaturated lipids, the main components of biological membranes, are particularly susceptible to the oxidative attack of reactive oxygen species. The peroxidation of unsaturated lipids, in our case 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), induces the structural reorganization of the membrane. We have employed a multi-technique approach to analyze typical properties of lipid bilayers, i.e., roughness, thickness, elasticity, and fluidity. We compared the alteration of the membrane properties upon initiated lipid peroxidation and examined the ability of flavonols, namely quercetin (QUE), myricetin (MCE), and myricitrin (MCI) at different molar fractions, to inhibit this change. Using Mass Spectrometry (MS) and Fourier Transform Infrared Spectroscopy (FTIR), we identified various carbonyl products and examined the extent of the reaction. From Atomic Force Microscopy (AFM), Force Spectroscopy (FS), Small Angle X-Ray Scattering (SAXS), and Electron Paramagnetic Resonance (EPR) experiments, we concluded that the membranes with inserted flavonols exhibit resistance against the structural changes induced by the oxidative attack, which is a finding with multiple biological implications. Our approach reveals the interplay between the flavonol molecular structure and the crucial membrane properties under oxidative attack and provides insight into the pathophysiology of cellular oxidative injury.
Design and Application of Daylight-Based Lighting Controller on LED Luminaire
Authors: Bunjongjit Sulee , Ananwattanaporn Santipont , Ngaopitakkul Atthapol , Jettanasen Chaiyan , Patcharoen Theerasak
Published: May 2020

This paper proposes a control circuit for Light Emitting Diode (LED) luminaire based on the amount of daylight. This system uses both natural daylight and artificial light from a luminaire to reach the desired illuminance on a working plane. The control circuit operates by receiving an illuminance value from a light sensor and comparing it with a set value in the microcontroller before limiting the light intensity of LED by sending a control Pulse Width Modulation (PWM) signal to the LED driver. In the experimental setup, the controller and a physical model of a working space were built in order to field test the LED daylight control circuit. Electrical characteristics such as voltage, current, and power were measured with a power meter. Illumination characteristics in terms of illuminance on a working plane were determined using a lux meter. The results from actual field tests revealed that this LED control circuit was able to reduce the power consumption of the lighting system while keeping the illuminance on the working plane at the standard value. Both simulation results and the actual experiment of the control circuit proved that it could be used to improve the energy efficiency of both newly installed and retrofitted lighting systems.
Finite Element Analysis of Traditional and New Fixation Techniques of the 3D-Printed Composite Interlocking Nail in Canine Femoral Shaft Fractures
Authors: Pitjamit Siwasit , Nakkiew Wasawat , Thongkorn Kriangkrai , Thanakulwattana Warinthorn , Thunsiri Kittiya
Published: May 2020

Since the removal of a metallic interlocking nail system leaves a blank cavity inside a healed bone, bioactive and biodegradation materials have been used instead to induce bone formation and eliminate complications of the material removal procedure. The previous study presented the possibility of an interlocking nail fabrication from polylactic acid (PLA), polycaprolactone (PCL), and hydroxyapatite (HA) using 3D printing, namely fused filament fabrication (FFF), for canine diaphyseal fractures. Therefore, a finite element analysis (FEA) was used to predict the maximum principal stress of this 3D-printed composite interlocking nail to stabilize a canine femoral fracture, and the biomechanical performance was evaluated for the treatment of canine femoral shaft fractures using both traditional and new fixation techniques. Three-dimensional FEA models were created, and the composite interlocking nail was tested for implant strength and stability. Three types of canine femoral shaft fracture (proximal shaft fracture, middle shaft fracture, and distal shaft fracture) fixed by traditional and new fixation techniques, consisting of two, four, and six locking screws, were analyzed with a multilevel factorial design technique. The maximum principal stresses of the composite interlocking nail were compared with each fixation technique. According to the multilevel factorial design, gap type, fracture gap, and fixation techniques are factors that affect the maximum principal stress of the composite interlocking nail for two and four locking screws. For six locking screws, all factors, including gap type, fracture gap, nail length, and fixation techniques, significantly affect the maximum principal stress. The use of a 3D-printed composite interlocking nail system with new fixation techniques demonstrated lower maximum principal stresses than the interlocking nail system that used a traditional fixation technique. The results of this study could help orthopedic veterinary surgeons to understand the biomechanical performances of traditional and new fixation techniques. Furthermore, surgeons may use the numerical results of this analysis to choose a fixation technique based on a patient’s condition.
Analysis of Hybrid Vector Beams Generated with a Detuned Q-Plate
Authors: Quiceno-Moreno Julio César , Marco David , Sánchez-López María del Mar , Solarte Efraín , Moreno Ignacio
Published: May 2020

We use a tunable commercial liquid-crystal device tuned to a quarter-wave retardance to study the generation and dynamics of different types of hybrid vector beams. The standard situation where the q-plate is illuminated by a Gaussian beam is compared with other cases where the input beam is a vortex or a pure vector beam. As a result, standard hybrid vector beams but also petal-like hybrid vector beams are generated. These beams are analyzed in the near field and compared with the far field distribution, where their hybrid nature is observed as a transformation of the intensity and polarization patterns. Analytical calculations and numerical results confirm the experiments. We include an approach that provides an intuitive physical explanation of the polarization patterns in terms of mode superpositions and their transformation upon propagation based on their different Gouy phase. The tunable q-plate device presents worthy advantages, since it allows a compact and efficient generation of pure and hybrid vector beams to study these effects.
Capturing the Swirling Vortex and the Impact of Ventilation Conditions on Small-Scale Fire Whirls
Authors: Fang Xiang , Yuen Anthony Chun Yin , Yeoh Guan Heng , Lee Eric Wai Ming , Cheung Sherman Chi P.
Published: May 2020

The fundamental flow structure and temperature distribution of small-scale fire whirls, including tangential and axial velocities, temperature variation, and air entrainment in the lower boundary layer, were successfully captured using a generic fire field model with large eddy simulation (LES) turbulence closure. Numerical predictions were validated thoroughly against two small-scale experimental measurements, where detailed temperature and velocity distributions were recorded. Good agreement between numerical and experimental results was achieved. Normalization was also performed to compare the numerical predictions with the empirical correlations by Lei et al. (2015) developed from medium-scale fire whirl measurements. The transient development stages of small-scale fire whirls and the impact of air entrainment on the stability of the fire whirls were also investigated based on the validated numerical results. The numerical validations showed the potential of the current LES fire field model in capturing the dynamic behaviour of the fire whirl plume and performing a quantitative analysis on its onset criteria and combustion dynamics in future.
Analysis of Extreme Temperature Events over the Iberian Peninsula during the 21st Century Using Dynamic Climate Projections Chosen Using Max-Stable Processes
Authors: Portero Serrano Javier , Acero Díaz Francisco Javier , García García José Agustín
Published: May 2020

Due to climate change, the Iberian Peninsula is suffering an increasing trend of extreme temperature events. The main objective of this study is to analyse this trends in frequency, duration and intensity of warm events and heat waves. The datasets used are 14 different regionalized dynamic climate projections. We choose the projections that present a spatial dependence similar to that of observed data. The spatial dependence is calculated by adjusting the data to max-stable processes. The observed data belong to the SPAIN02 grid for the period 1961–2000. We apply the Mann-Kendall test and the Theil-Sen estimator to calculate model trends in the future period (2011–2099). We have studied future extreme temperature events using two different definitions. One varying the threshold for each period and the other keeping it constant. The results show that the variability of maximum temperatures is decreasing for the western region of the Peninsula, while the Mediterranean area will see an increase in this variability. There will be an increase in the frequency of warm events for the southwestern corner of the Peninsula. Also, maximum temperatures will be higher in this area at the end of the century. However, in the Mediterranean region the warm events will last longer. Heat waves will be more frequent throughout the territory and more lasting in the Mediterranean area. We also found that studying extreme events using a varying threshold allows these events to be studied from the point of view of the variability of maximum temperatures, while if the study is carried out maintaining the threshold constant the results will be more direct.
The Application of a Decision Tree and Stochastic Forest Model in Summer Precipitation Prediction in Chongqing
Authors: Xiang Bo , Zeng Chunfen , Dong Xinning , Wang Jiayue
Published: May 2020

Meteorological disasters are the result of the interaction of multiple factors and multiple systems. In order to improve the accuracy of prediction, it is necessary not only to consider the characteristics and cycles of each subsystem, but also to study the interaction of all systems. Based on the summer precipitation data and 130 circulation indexes of 34 national meteorological observation stations in Chongqing from 1961 to 2010, the prediction model of Chongqing summer precipitation was established based on the decision tree and the stochastic forest algorithm based on machine learning, and the prediction test of 2011–2018 was carried out independently by the model. Compared with the results of the single-factor prediction model, the trend consistency rate increased by 37.5% and 12.5% respectively. In addition, when using the random forest model to predict summer precipitation in Chongqing from 2014 to 2018, the 5-year average Ps, Cc and PC scores were 84.6, 0.27 and 67.1, respectively, which were significantly improved compared with 72.4, −0.12 and 52.9 of the current climate forecasting methods, and the forecast quality of the random forest was relatively stable. The multi-system collaborative impact model based on decision tree and random forest algorithm can achieve high accuracy and stability. Thus, this method can not only be an effective means for the diagnosis and prediction of climate causes, but also has a good theoretical and practical value for the prediction of extreme disasters.
Air Quality in Brno City Parks
Authors: Huzlík Jiří , Hegrová Jitka , Effenberger Karel , Ličbinský Roman , Brtnický Martin
Published: May 2020

Parks embody an important element of urban infrastructure and a basic type of public space that shapes the overall character of a city. They form a counterweight to built-up areas and public spaces with paved surfaces. In this context, parks compensate for the lack of natural, open landscapes in cities and thus have a fundamental impact on the quality of life of their inhabitants. For this reason, it is important to consider the quality of the environment in urban parks, air quality in particular. Concentrations of gaseous pollutants, namely, nitric oxide (NO), nitrogen dioxide (NO2), and ozone (O3), were measured in parks of Brno, the second-largest city in the Czech Republic. Relevant concentration values of PM10 solids were determined continuously via the nephelometric method, followed by gravimetric method-based validation. The results obtained through the measurement of wind direction, wind speed, temperature, and relative humidity were used to identify potential sources of air pollution in parks. The “openair” and “openairmaps” packages from the OpenSource software R v. 3.6.2 were employed to analyze the effect of meteorological conditions on air pollution. Local polar concentration maps found use in localizing the most serious sources of air pollution within urban parks. The outcomes of the analyses show that the prevailing amount of the pollution determined at the measuring point most likely originates from the crossroads near the sampled localities. At the monitored spots, the maximum concentrations of pollutants are reached especially during the morning rush hour. The detailed time and spatial course of air pollution in the urban parks were indicated in the respective concentration maps capturing individual pollutants. Significantly increased concentrations of nitrogen oxides were established in a locality situated near a busy road (with the traffic intensity of 33,000 vehicles/d); this scenario generally applied to colder weather. The highest PM10 concentrations were measured at the same location and at an average temperature that proved to be the lowest within the entire set of measurements. In the main city park, unlike other localities, higher concentrations of PM10 were measured in warmer weather; such an effect was probably caused by the park being used to host barbecue parties.
Melleins—Intriguing Natural Compounds
Authors: Reveglia Pierluigi , Masi Marco , Evidente Antonio
Published: May 2020

Melleins are 3,4-dihydroisocoumarins mainly produced by fungi, but also by plants, insects and bacteria. These specialized metabolites play important roles in the life cycles of the producers and they are involved in many biochemical and ecological processes. This review outlines the isolation and chemical and biological characterizations of natural-occurring melleins from the first report of (R)-mellein in 1933 to the most recent advances in their characterization in 2019. In addition, the pathways that could be involved in mellein biosynthesis are discussed, along with the enzymes and genes involved.
Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain
Authors: Khaliulin Igor , Kartawy Maryam , Amal Haitham
Published: May 2020

Nitric oxide (NO) represents an important signaling molecule which modulates the functions of different organs, including the brain. S-nitrosylation (SNO), a post-translational modification that involves the binding of the NO group to a cysteine residue, is a key mechanism of nitrergic signaling. Most of the experimental studies are carried out on male animals. However, significant differences exist between males and females in the signaling mechanisms. To investigate the sex differences in the SNO-based regulation of biological functions and signaling pathways in the cortices of 6–8-weeks-old mice, we used the mass spectrometry technique, to identify S-nitrosylated proteins, followed by large-scale computational biology. This work revealed significant sex differences in the NO and SNO-related biological functions in the cortices of mice for the first-time. The study showed significant SNO-induced enrichment of the synaptic processes in female mice, but enhanced SNO-related cytoskeletal processes in the male mice. Proteins, which were S-nitrosylated in the cortices of mice of both groups, were more abundant in the female brain. Finally, we investigated the shared molecular processes that were found in both sexes. This study presents a mechanistic insight into the role of S-nitrosylation in both sexes and provides strong evidence of sex difference in many biological processes and signalling pathways, which will open future research directions on sex differences in neurological disorders.
Inflammatory and Oxidative Stress Markers—Mirror Tools in Rheumatoid Arthritis
Authors: Mititelu Radu Răzvan , Pădureanu Rodica , Băcănoiu Manuela , Pădureanu Vlad , Docea Anca Oana , Calina Daniela , Barbulescu Andreea Lili , Buga Ana Maria
Published: May 2020

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease, associated with significant morbidity, mainly due to progressive damage and consequent disability. Oxidative stress is an important part of RA pathophysiology, as in autoimmune disease the interaction between immune response and endogenous/exogenous antigens subsequently induce the production of reactive oxygen species. The oxidative stress process seems to be positively strongly correlated with inflammation and accelerated joint destruction. We were asking ourselves if the oxidative stress biomarkers are the mirror tools of disease activity, outcome, and inflammation level in a group of RA patients under standard or biological therapy compared to healthy age-matched controls. In order to do this, the oxidative stress damage biomarkers (lipids peroxide and protein carbonyl level), antioxidant defense capacity, and pro-inflammatory status of plasma were quantified. In this study, we took into account the complete picture of RA diseases and assessed, for the first time, the inflammatory level in correlation with the oxidative stress level and antioxidant capacity of RA patients. Our results revealed that protein oxidation through carbonylation is significantly increased in RA groups compared to controls, and both protein carbonyl Pcarb and thiobarbituric acid reactive substance (TBARS) are reliable markers of ROS damage. Therefore, it is unanimous that neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PltLR) correlated with Pcarb, and TBARS can provide a view of the complex phenomenon represented by proteins/lipids damage, key contributors to disease outcome, and an increased awareness should be attributed to these biomarkers.
Gaze Palsy as a Manifestation of Todd’s Phenomenon: Case Report and Review of the Literature
Authors: Olaciregui Dague Karmele , Dafotakis Manuel , Schulz Jörg , Surges Rainer
Published: May 2020

Background: Though Todd’s phenomenon (TP) is a relatively rare occurrence, its correct identification is of key diagnostic and therapeutic importance as a stroke mimic. Here we describe a case of isolated gaze palsy as a manifestation of TP, discuss periictal gaze abnormalities as lateralizing sign involving the frontal eye field (FEF), and present a narrative literature review. Methods: We reviewed the main features of the case and conducted a structured literature search of TP and gaze palsy using PubMed. We restricted the search to publications in English, Spanish, French, and German. Case presentation: A 71-year-old male with a history of right frontotemporal subarachnoid hemorrhage was admitted to the Emergency Department of our institution after suffering a first unprovoked focal to bilateral tonic-clonic seizure with ictal gaze deviation to the left. Cranial imaging showed no signs of ischemia, intracerebral hemorrhage, or tumor. The patient presented the following postictal features: involuntary eye deviation to the right due to left-sided gaze palsy and disorientation in time with preserved responsiveness. Eye movements were normal three days later. We concluded that the patient suffered from new-onset epilepsy due to sequelae following the right frontotemporal subarachnoid hemorrhage, affecting the FEF with contralateral ictal gaze deviation, and postictal gaze palsy with ipsilateral eye deviation as an unusual Todd’s phenomenon. Conclusion: Unusual manifestations of TP are uncommon but clinically highly relevant, as they can mimic stroke or epileptic status and are decisive in the diagnostic and therapeutic decision-making process. Though postictal gaze palsy has been reported associated with other deficits, this constitutes, to our knowledge, the first report of isolated gaze palsy as a form of TP. Further research into the underlying causes is needed. Ictal contralateral gaze and head deviation, and probably postictal ipsilateral gaze deviation if present, are very helpful for the lateralization of the seizure-onset zone.
Deep Brain Stimulation for Gilles de la Tourette Syndrome: Toward Limbic Targets
Authors: Servello Domenico , Galbiati Tommaso Francesco , Balestrino Roberta , Iess Guglielmo , Zekaj Edvin , De Michele Sara , Porta Mauro
Published: May 2020

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by tics and, frequently, psychiatric and behavioral comorbidities. Above all, obsessive compulsive disorder/behavior (OCD/OCB) influences the clinical picture and has a severe impact on quality of life, eventually more than the tics themselves. Deep brain stimulation (DBS) is an effective therapy in selected, refractory cases. Clinical response to DBS may vary according to the clinical picture, comorbidities, and to the anatomical target. This retrospective study compares the results obtained from DBS in the ventralis oralis/centromedian-parascicular nucleus of the thalamus (Voi-Cm/Pf) (41 patients) and antero-medial Globus Pallidus internus (am-GPi) (14 patients), evaluating clinical response over time by means of Yale Global Tic Severity Scale (YGTSS) and Yale–Brown Obsessive-Compulsive Scale (YBOCS) scores over a period of 48 months. A significant and stable improvement in the YGTSS and YBOCS has been obtained in both groups (p < 0.001). There was a significant difference in YBOCS improvement over time between the am-GPi group and the Voi-Cm/Pf group, indicating a better and faster control of OCD/OCB symptoms in the former group. The ratio of hardware removal was 23% and limited to 13 patients in the Voi-Cm/Pf group. These results confirm that DBS is an effective therapy in treating GTS and suggest that the am-GPi might be superior to Voi-Cm/Pf in alleviating comorbid OCD/OCB.
Modulation of Fibers to Motor Cortex during Thalamic DBS in Tourette Patients Correlates with Tic Reduction
Authors: Andrade Pablo , Heiden Petra , Hoevels Moritz , Schlamann Marc , Baldermann Juan C. , Huys Daniel , Visser-Vandewalle Veerle
Published: May 2020

Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus–nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of stimulation-dependent connectivity between CM-Voi and the motor cortex, and in particular, an increased density of projections to the presupplementary motor area (preSMA). Non-responder patients displayed the largest amount of active fibers projecting into cortical areas other than motor cortex compared to responder patients. These findings support the notion that an abnormal connectivity of thalamocortical pathways underlies TS, and that modulation of these circuits through DBS could restore the function and reduce symptoms.
Co-Expression of Androgen Receptor and Cathepsin D Defines a Triple-Negative Breast Cancer Subgroup with Poorer Overall Survival
Authors: Mansouri Hanane , Alcaraz Lindsay B. , Mollevi Caroline , Mallavialle Aude , Jacot William , Boissière-Michot Florence , Simony-Lafontaine Joelle , Laurent-Matha Valérie , Roger Pascal , Liaudet-Coopman Emmanuelle , Guiu Séverine
Published: May 2020

Background: In the triple-negative breast cancer (TNBC) group, the luminal androgen receptor subtype is characterized by expression of androgen receptor (AR) and lack of estrogen receptor and cytokeratin 5/6 expression. Cathepsin D (Cath-D) is overproduced and hypersecreted by breast cancer (BC) cells and is a poor prognostic marker. We recently showed that in TNBC, Cath-D is a potential target for antibody-based therapy. This study evaluated the frequency of AR/Cath-D co-expression and its prognostic value in a large series of patients with non-metastatic TNBC. Methods: AR and Cath-D expression was evaluated by immunohistochemistry in 147 non-metastatic TNBC. The threshold for AR positivity (AR+) was set at ≥1% of stained cells, and the threshold for Cath-D positivity (Cath-D+) was moderate/strong staining intensity. Lymphocyte density, macrophage infiltration, PD-L1 and programmed cell death (PD-1) expression were assessed. Results: Scarff-Bloom-Richardson grade 1–2 and lymph node invasion were more frequent, while macrophage infiltration was less frequent in AR+/Cath-D+ tumors (62.7%). In multivariate analyses, higher tumor size, no adjuvant chemotherapy and AR/Cath-D co-expression were independent prognostic factors of worse overall survival. Conclusions: AR/Cath-D co-expression independently predicted overall survival. Patients with TNBC in which AR and Cath-D are co-expressed could be eligible for combinatory therapy with androgen antagonists and anti-Cath-D human antibodies.
Mechanisms of Long Non-Coding RNAs in Cancers and Their Dynamic Regulations
Authors: Zhang Xiao-Zhen , Liu Hao , Chen Su-Ren
Published: May 2020

Long non-coding RNA (lncRNA), which is a kind of noncoding RNA, is generally characterized as being more than 200 nucleotide transcripts in length. LncRNAs exhibit many biological activities, including, but not limited to, cancer development. In this review, a search of the PubMed database was performed to identify relevant studies published in English. The term “lncRNA or long non-coding RNA” was combined with a range of search terms related to the core focus of the review: mechanism, structure, regulation, and cancer. The eligibility of the retrieved studies was mainly based on the abstract. The decision as to whether or not the study was included in this review was made after a careful assessment of its content. The reference lists were also checked to identify any other study that could be relevant to this review. We first summarized the molecular mechanisms of lncRNAs in tumorigenesis, including competing endogenous RNA (ceRNA) mechanisms, epigenetic regulation, decoy and scaffold mechanisms, mRNA and protein stability regulation, transcriptional and translational regulation, miRNA processing regulation, and the architectural role of lncRNAs, which will help a broad audience better understand how lncRNAs work in cancer. Second, we introduced recent studies to elucidate the structure of lncRNAs, as there is a link between lncRNA structure and function and visualizing the architectural domains of lncRNAs is vital to understanding their function. Third, we explored emerging evidence for regulators of lncRNA expression, lncRNA turnover, and lncRNA modifications (including 5-methylcytidine, N6-methyladenosine, and adenosine to inosine editing), highlighting the dynamics of lncRNAs. Finally, we used autophagy in cancer as an example to interpret the diverse mechanisms of lncRNAs and introduced clinical trials of lncRNA-based cancer therapies.
Beyond MicroRNAs: Emerging Role of Other Non-Coding RNAs in HPV-Driven Cancers
Authors: Casarotto Mariateresa , Fanetti Giuseppe , Guerrieri Roberto , Palazzari Elisa , Lupato Valentina , Steffan Agostino , Polesel Jerry , Boscolo-Rizzo Paolo , Fratta Elisabetta
Published: May 2020

Persistent infection with high-risk Human Papilloma Virus (HPV) leads to the development of several tumors, including cervical, oropharyngeal, and anogenital squamous cell carcinoma. In the last years, the use of high-throughput sequencing technologies has revealed a number of non-coding RNA (ncRNAs), distinct from micro RNAs (miRNAs), that are deregulated in HPV-driven cancers, thus suggesting that HPV infection may affect their expression. However, since the knowledge of ncRNAs is still limited, a better understanding of ncRNAs biology, biogenesis, and function may be challenging for improving the diagnosis of HPV infection or progression, and for monitoring the response to therapy of patients affected by HPV-driven tumors. In addition, to establish a ncRNAs expression profile may be instrumental for developing more effective therapeutic strategies for the treatment of HPV-associated lesions and cancers. Therefore, this review will address novel classes of ncRNAs that have recently started to draw increasing attention in HPV-driven tumors, with a particular focus on ncRNAs that have been identified as a direct target of HPV oncoproteins.
Harnessing Gene Expression Profiles for the Identification of Ex Vivo Drug Response Genes in Pediatric Acute Myeloid Leukemia
Authors: Cucchi David G.J. , Bachas Costa , van den Heuvel-Eibrink Marry M. , Arentsen-Peters Susan T.C.J.M. , Kwidama Zinia J. , Schuurhuis Gerrit J. , Assaraf Yehuda G. , de Haas Valérie , Kaspers Gertjan J.L. , Cloos Jacqueline
Published: May 2020

Novel treatment strategies are of paramount importance to improve clinical outcomes in pediatric AML. Since chemotherapy is likely to remain the cornerstone of curative treatment of AML, insights in the molecular mechanisms that determine its cytotoxic effects could aid further treatment optimization. To assess which genes and pathways are implicated in tumor drug resistance, we correlated ex vivo drug response data to genome-wide gene expression profiles of 73 primary pediatric AML samples obtained at initial diagnosis. Ex vivo response of primary AML blasts towards cytarabine (Ara C), daunorubicin (DNR), etoposide (VP16), and cladribine (2-CdA) was associated with the expression of 101, 345, 206, and 599 genes, respectively (p < 0.001, FDR 0.004–0.416). Microarray based expression of multiple genes was technically validated using qRT-PCR for a selection of genes. Moreover, expression levels of BRE, HIF1A, and CLEC7A were confirmed to be significantly (p < 0.05) associated with ex vivo drug response in an independent set of 48 primary pediatric AML patients. We present unique data that addresses transcriptomic analyses of the mechanisms underlying ex vivo drug response of primary tumor samples. Our data suggest that distinct gene expression profiles are associated with ex vivo drug response, and may confer a priori drug resistance in leukemic cells. The described associations represent a fundament for the development of interventions to overcome drug resistance in AML, and maximize the benefits of current chemotherapy for sensitive patients.
Multi-Modal PET and MR Imaging in the Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM) Model for Initial In Vivo Testing of Target-Specific Radioligands
Authors: Winter Gordon , Koch Andrea B. F. , Löffler Jessica , Lindén Mika , Solbach Christoph , Abaei Alireza , Li Hao , Glatting Gerhard , Beer Ambros J. , Rasche Volker
Published: May 2020

The validation of novel target-specific radioligands requires animal experiments mostly using mice with xenografts. A pre-selection based on a simpler in vivo model would allow to reduce the number of animal experiments, in accordance with the 3Rs principles (reduction, replacement, refinement). In this respect, the chick embryo or hen’s egg test–chorioallantoic membrane (HET-CAM) model is of special interest, as it is not considered an animal until day 17. Thus, we evaluated the feasibility of quantitative analysis of target-specific radiotracer accumulation in xenografts using the HET-CAM model and combined positron emission tomography (PET) and magnetic resonance imaging (MRI). For proof-of-principle we used established prostate-specific membrane antigen (PSMA)-positive and PSMA-negative prostate cancer xenografts and the clinically widely used PSMA-specific PET-tracer [68Ga]Ga-PSMA-11. Tracer accumulation was quantified by PET and tumor volumes measured with MRI (n = 42). Moreover, gamma-counter analysis of radiotracer accumulation was done ex-vivo. A three- to five-fold higher ligand accumulation in the PSMA-positive tumors compared to the PSMA-negative tumors was demonstrated. This proof-of-principle study shows the general feasibility of the HET-CAM xenograft model for target-specific imaging with PET and MRI. The ultimate value for characterization of novel target-specific radioligands now has to be validated in comparison to mouse xenograft experiments.
A Novel Role for NUAK1 in Promoting Ovarian Cancer Metastasis through Regulation of Fibronectin Production in Spheroids
Authors: Fritz Jamie Lee , Collins Olga , Saxena Parima , Buensuceso Adrian , Ramos Valdes Yudith , Francis Kyle E. , Brown Kevin R. , Larsen Brett , Colwill Karen , Gingras Anne-Claude , Rottapel Robert , Shepherd Trevor G.
Published: May 2020

Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabilization. We next investigated NUAK1 function in EOC cells. Ectopic NUAK1-overexpressing EOC cell lines had increased adhesion, whereas the reverse was seen in OVCAR8-NUAK1KO cells. In fact, cells with NUAK1 loss generate spheroids with reduced integrity, leading to increased cell death after long-term culture. Following transcriptome analysis, we identified reduced enrichment for cell interaction gene expression pathways in OVCAR8-NUAK1KO spheroids. In fact, the FN1 gene, encoding fibronectin, exhibited a 745-fold decreased expression in NUAK1KO spheroids. Fibronectin expression was induced during native spheroid formation, yet this was completely lost in NUAK1KO spheroids. Co-incubation with soluble fibronectin restored the compact spheroid phenotype to OVCAR8-NUAK1KO cells. In a xenograft model of intraperitoneal metastasis, NUAK1 loss extended survival and reduced fibronectin expression in tumours. Thus, we have identified a new mechanism controlling EOC metastasis, through which LKB1-NUAK1 activity promotes spheroid formation and secondary tumours via fibronectin production.
Proposal of a Two-Tier System in Grouping Adenocarcinoma of the Uterine Cervix
Authors: Machida Hiroko , Matsuo Koji , Matsuzaki Shinya , Yamagami Wataru , Ebina Yasuhiko , Kobayashi Yoichi , Tabata Tsutomu , Kaneuchi Masanori , Nagase Satoru , Enomoto Takayuki , Mikami Mikio
Published: May 2020

(1) Background: This study examined the use of a two-tier system in grouping cervical adenocarcinoma for survival discrimination. (2) Methods: A nationwide retrospective observational cohort study was conducted using the Japan Society of Gynecologic Oncology tumor registry database from 2001 to 2015 (n = 86,754). Adenocarcinoma subtypes were grouped as type 1 (endocervical usual type and endometrioid) or type 2 (serous, clear, mucinous, and not otherwise specified), based on their relative survival compared with that of squamous tumors. (3) Results: The majority of the adenocarcinoma cases were type 1 (n = 10,121) versus type 2 tumors (n = 5157). Type 2 tumors were more likely to be old and have stage IV disease than those with squamous tumors. The number of type 2 tumors increased from 2001 to 2014 (106.1% relative increase, p < 0.001). Type 2 tumors had disproportionally poorer survival compared to other types (5-year survival rates: 68.9% for type 2, 75.4% for type 1, and 78.0% for squamous; p < 0.001). On multivariate analysis, type 2 tumors remained an independent prognostic factor associated with decreased survival compared with squamous (adjusted hazard ratio 2.00, 95% CI 1.84–2.15, p < 0.001). (4) Conclusion: The survival of cervical adenocarcinoma varies largely across the histological subtypes, and the proposed two-tier grouping may be useful for survival discrimination.
Simulation and Optimization of the CWPO Process by Combination of Aspen Plus and 6-Factor Doehlert Matrix: Towards Autothermal Operation
Authors: Diaz de Tuesta Jose L. , Quintanilla Asunción , Moreno Daniel , Ferro Víctor R. , Casas Jose A.
Published: May 2020

This work aims to present an industrial perspective on Catalytic Wet Peroxide Oxidation (CWPO) technology. Herein, process simulation and experimental design have been coupled to study the optimal process conditions to ensure high-performance oxidation, minimum H2O2 consumption and maximum energetic efficiency in an industrial scale CWPO unit. The CWPO of phenol in the presence of carbon black catalysts was studied as a model process in the Aspen Plus® v11 simulator. The kinetic model implemented, based on 30 kinetic equations with 11 organic compounds and H2O2 involvement, was valid to describe the complex reaction network and to reproduce the experimental results. The computer experiments were designed on a six-factor Doehlert Matrix in order to describe the influence of the operating conditions (i.e., the different process temperatures, inlet chemical oxygen demands, doses of H2O2 and space time) on each selected output response (conversion, efficiency of H2O2 consumption and energetic efficiency) by a quadratic model. The optimization of the WPO performance by a multi-criteria function highlighted the inlet chemical oxygen demand as the most influential operating condition. It needed to have values between 9.5 and 24 g L−1 for autothermal operation to be sustained under mild operating conditions (reaction temperature: 93–130 °C and pressure: 1–4 atm) and with a stoichiometric dose of H2O2.
Fabrication of ZnO-Fe-MXene Based Nanocomposites for Efficient CO2 Reduction
Authors: Kannan Karthik , Sliem Mostafa H. , Abdullah Aboubakr M. , Sadasivuni Kishor Kumar , Kumar Bijandra
Published: May 2020

A ZnO-Fe-MXene nanocomposite was fabricated and examined with diverse spectroscopic techniques. The hexagonal structure of ZnO, MXene, and ZnO-Fe-MXene nanocomposites were validated through XRD. FTIR showed the characteristic vibrational frequencies of ZnO and MXene. The micrographs of the SEM showed nanoparticles with a flower-like structure. The electrocatalytic reduction efficiency of ZnO-Fe-MXene nanocomposite was analyzed through cyclic voltammetry and electrochemical impedance spectroscopy methods. The ZnO-Fe-MXene electrode was confirmed to have a high current density of 18.75 mA/cm2 under a CO2 atmosphere. Nyquist plots also illustrated a decrease in the impedance of the ZnO-Fe-MXene layer, indicating fast charge transfer between the Zn and MXene layers. Additionally, this electrochemical study highlights new features of ZnO-Fe-MXene for CO2 reduction.
Structure, Acidity, and Redox Aspects of VOx/ZrO2/SiO2 Catalysts for the n-Butane Oxidative Dehydrogenation
Authors: Sánchez-García José-Luis , Handy Brent E. , Ávila-Hernández Ilse N. , Rodríguez Angel G. , García-Alamilla Ricardo , Cardenas-Galindo Maria-Guadalupe
Published: May 2020

ZrOx/SiO2 and VOx/ZrOx/SiO2 catalysts (5 wt %–25 wt % Zr, 4 wt % V) were prepared by grafting zirconium and vanadium alkoxides on Aerosil 380. All samples were characterized by temperature programmed reduction, N2 physisorption, X-ray diffraction, Raman spectroscopy, and ammonia adsorption microcalorimetry. Tetragonal ZrO2 and zircon (ZrSiO4) were present at 25 wt % Zr, but only amorphous zirconia overlayer existed for lower loadings. At lower Zr loadings (5 wt %–10 wt % Zr), exposed silica surface leads to V2O5 crystallites and isolated VO4 species, although V reducibility behavior changes, from being similar to VOx/SiO2 (5 wt % Zr) to showing VOx/ZrO2 behavior at 10 wt % Zr, and a diminished total amount of reducible V. Highly acidic ZrO2 sites are covered by the vanadium grafting, forming weaker sites (60–100 kJ/mol NH3 adsorption strength). Catalytic conversion and selectivity for the oxidative dehydrogenation of n-butane (673 K, n-C4/O2 = 2.2) over VOx/ZrOx/SiO2 show that 1,3-butadiene is favored over cis-2-butene and trans-2-butene, although there is some selectivity to the 2-butenes when VOx/ZrO2 behavior is evident. At low Zr loadings, butadiene formed during reaction acts as the diene species in a Diels–Alder reaction and gives rise to a cyclic compound that undergoes further dehydrogenation to produce benzaldehyde.
TNFα Rescues Dendritic Cell Development in Hematopoietic Stem and Progenitor Cells Lacking C/EBPα
Authors: Anirudh Subramanian , Rosenberger Angelika , Schwarzenberger Elke , Schaefer Carolin , Strobl Herbert , Zebisch Armin , Sill Heinz , Wölfler Albert
Published: May 2020

Dendritic cells (DCs) are crucial effectors of the immune system, which are formed from hematopoietic stem and progenitor cells (HSPCs) by a multistep process regulated by cytokines and distinct transcriptional mechanisms. C/EBPα is an important myeloid transcription factor, but its role in DC formation is not well defined. Using a CebpaCre-EYFP reporter mouse model, we show that the majority of splenic conventional DCs are derived from Cebpa-expressing HSPCs. Furthermore, HSPCs isolated from Cebpa knockout (KO) mice exhibited a marked reduced ability to form mature DCs after in vitro culture with FLT3L. Differentiation analysis revealed that C/EBPα was needed for the formation of monocytic dendritic progenitors and their transition to common dendritic progenitors. Gene expression analysis and cytokine profiling of culture supernatants showed significant downregulation of inflammatory cytokines, including TNFα and IL-1β as well as distinct chemokines in KO HSPCs. In addition, TNFα-induced genes were among the most dysregulated genes in KO HSPCs. Intriguingly, supplementation of in vitro cultures with TNFα at least partially rescued DC formation of KO HSPCs, resulting in fully functional, mature DCs. In conclusion, these results reveal an important role of C/EBPα in early DC development, which in part can be substituted by the inflammatory cytokine TNFα.