bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptomic Evidence of Molecular Mechanisms Underlying the Response of Lactobacillus plantarum WCFS1 to Hydroxytyrosol
Authors: Reverón Inés , Plaza-Vinuesa Laura , Santamaría Laura , Oliveros Juan Carlos , de las Rivas Blanca , Muñoz Rosario , López de Felipe Félix
Published: May 2020

This study was aimed to gain new insights into the molecular mechanisms used by Lactobacillus plantarum WCFS1 to respond to hydroxytyrosol (HXT), one of the main and health-relevant plant phenolics present in olive oil. To this goal, whole genome transcriptomic profiling was used to better understand the contribution of differential gene expression in the adaptation to HXT by this microorganism. The transcriptomic profile reveals an HXT-triggered antioxidant response involving genes from the ROS (reactive oxygen species) resistome of L. plantarum, genes coding for H2S-producing enzymes and genes involved in the response to thiol-specific oxidative stress. The expression of a set of genes involved in cell wall biogenesis was also upregulated, indicating that this subcellular compartment was a target of HXT. The expression of several MFS (major facilitator superfamily) efflux systems and ABC-transporters was differentially affected by HXT, probably to control its transport across the membrane. L. plantarum transcriptionally reprogrammed nitrogen metabolism and involved the stringent response (SR) to adapt to HXT, as indicated by the reduced expression of genes involved in cell proliferation or related to the metabolism of (p)ppGpp, the molecule that triggers the SR. Our data have identified, at genome scale, the antimicrobial mechanisms of HXT action as well as molecular mechanisms that potentially enable L. plantarum to cope with the effects of this phenolic compound.
Intensity and Driving Forces of Land Abandonment in Eastern Poland
Authors: Zgłobicki Wojciech , Karczmarczuk Kamil , Baran-Zgłobicka Bogusława
Published: May 2020

Agricultural land is an important natural resource and forms the basis for food production. Global and local socio-economic and environmental changes are often the driving forces of changes in land cover and land use. Land abandonment in rural areas is one of the processes observed in Europe today and usually leads to increased afforestation. The intensity of this process in Central Europe is linked to the political and economic changes that took place at the end of the 20th century. The study objective was to identify the natural and socio-economic factors of this process in Lublin Province—a major region of agricultural production in Poland. From 1990 to 2018, over 130,000 ha were excluded from agricultural use, which represents 7% of the arable land in 1990. Land abandonment showed considerable spatial differences when comparing different counties: its magnitude ranged from 4% to 13% of the county area. At the same time, due to the specific type of land use in the province (small farm holdings divided into several fields), the intensity of land abandonment was underestimated when based on overview data (CORINE). It was observed that the intensity of this process was correlated with the natural conditions (topography, soils) for agricultural production and the socio-economic characteristics (area of arable land, forest cover changes, farm size) of the counties as well as the absorption of Common Agricultural Policy funds.
Emotion Recognition Using Convolutional Neural Network with Selected Statistical Photoplethysmogram Features
Authors: Lee MinSeop , Lee Yun Kyu , Lim Myo-Taeg , Kang Tae-Koo
Published: May 2020

Emotion recognition research has been conducted using various physiological signals. In this paper, we propose an efficient photoplethysmogram-based method that fuses the deep features extracted by two deep convolutional neural networks and the statistical features selected by Pearson’s correlation technique. A photoplethysmogram (PPG) signal can be easily obtained through many devices, and the procedure for recording this signal is simpler than that for other physiological signals. The normal-to-normal (NN) interval values of heart rate variability (HRV) were utilized to extract the time domain features, and the normalized PPG signal was used to acquire the frequency domain features. Then, we selected features that correlated highly with an emotion through Pearson’s correlation. These statistical features were fused with deep-learning features extracted from a convolutional neural network (CNN). The PPG signal and the NN interval were used as the inputs of the CNN to extract the features, and the total concatenated features were utilized to classify the valence and the arousal, which are the basic parameters of emotion. The Database for Emotion Analysis using Physiological signals (DEAP) was chosen for the experiment, and the results demonstrated that the proposed method achieved a noticeable performance with a short recognition interval.
Effects of Upper-Limb, Lower-Limb, and Full-Body Compression Garments on Full Body Kinematics and Free-Throw Accuracy in Basketball Players
Authors: Wong Duo Wai-Chi , Lam Wing-Kai , Chen Tony Lin-Wei , Tan Qitao , Wang Yan , Zhang Ming
Published: May 2020

Compression garments can enhance performance and promote recovery in athletes. Different body coverage with compression garments may impose distinct effects on kinematic movement mechanics and thus basketball free-throw accuracy. The objective of this study was to examine basketball free-throw shooting accuracy, consistency and the range of motion of body joints while wearing upper-, lower- and full-body compression garments. Twenty male basketball players performed five blocks of 20 basketball free-throw shooting trials in each of the following five compression garment conditions: control-pre, top, bottom, full (top + bottom) and control-post. All conditions were randomized except pre- and post-control (the first and last conditions). Range of motion of was acquired by multiple inertial measurement units. Free-throw accuracy and the coefficient of variation were also analyzed. Players wearing upper-body or full-body compression garments had significantly improved accuracy by 4.2% and 5.9%, respectively (p < 0.05), but this difference was not observed with shooting consistency. Smaller range of motion of head flexion and trunk lateral bending (p < 0.05) was found in the upper- and full-body conditions compared to the control-pre condition. These findings suggest that an improvement in shooting accuracy could be achieved by constraining the range of motion through the use of upper-body and full-body compression garments.
Exercise-Induced Hemodynamic Changes in Muscle Tissue: Implication of Muscle Fatigue
Authors: Tan Qitao , Wang Yan , Chen Tony Lin-Wei , Wong Duo Wai-Chi , Yan Fei , Li Zengyong , Zhang Ming
Published: May 2020

This research aims to investigate the development of muscle fatigue and the recovery process revealed by tissue oxygenation. The tissue hemodynamics were measured by near-infrared spectroscopy (NIRS) during a 30-min pre-exercise rest, a 40-cycle heel-lift exercise and a 30-min post-exercise recovery. Wavelet transform was used to obtain the normalized wavelet energy in six frequency intervals (I–VI) and inverse wavelet transform was applied to extract exercise-induced oscillations from the hemodynamic signals. During the exercise phase, the contraction-related oscillations in the total hemoglobin signal (ΔtHb) showed a decreasing trend while the fluctuations in the tissue oxygenation index (TOI) displayed an increasing tendency. The mean TOI value was significantly higher (p < 0.001) under recovery (65.04% ± 2.90%) than that under rest (62.35% ± 3.05%). The normalized wavelet energy of the ΔtHb signal in frequency intervals I (p < 0.001), II (p < 0.05), III (p < 0.05) and IV (p < 0.01) significantly increased by 43.4%, 23.6%, 18.4% and 21.6% during the recovery than that during the pre-exercise rest, while the value in interval VI (p < 0.05) significantly decreased by 16.6%. It could be concluded that NIRS-derived hemodynamic signals can provide valuable information related to muscle fatigue and recovery.
A Study of Cellular Traffic Data Prediction by Kernel ELM with Parameter Optimization
Authors: Zheng Xiaoliang , Lai Wenhao , Chen Hualiang , Fang Shen , Li Ziqiao
Published: May 2020

Accurate and efficient prediction of mobile network traffic in a public setting with changing flow of people can not only ensure a stable network but also help operators make resource scheduling decisions before reasonably allocating resources. Therefore, this paper proposes a method based on kernel extreme learning machine (kELM) for traffic data prediction. Particle swarm optimization (PSO), multiverse optimizer (MVO), and moth–flame optimization (MFO) were adopted to optimize kELM parameters for finding the best solution. To verify the predictive performance of the kernel ELM model, backpropagation (BP) neural network, v-support vector regression (vSVR), and ELM were also applied to traffic prediction, and the results were compared with kELM. Experimental results showed that the smallest mean absolute percentage error in the test (11.150%) was achieved when kELM was optimized by MFO with Gaussian as the kernel function, that is, the prediction result of MFO-kELM was the best. This study can provide significant guidance for network stability and resource conservation.
Static Analysis for ECMAScript String Manipulation Programs
Authors: Arceri Vincenzo , Mastroeni Isabella , Xu Sunyi
Published: May 2020

In recent years, dynamic languages, such as JavaScript or Python, have been increasingly used in a wide range of fields and applications. Their tricky and misunderstood behaviors pose a great challenge for static analysis of these languages. A key aspect of any dynamic language program is the multiple usage of strings, since they can be implicitly converted to another type value, transformed by string-to-code primitives or used to access an object-property. Unfortunately, string analyses for dynamic languages still lack precision and do not take into account some important string features. In this scenario, more precise string analyses become a necessity. The goal of this paper is to place a first step for precisely handling dynamic language string features. In particular, we propose a new abstract domain approximating strings as finite state automata and an abstract interpretation-based static analysis for the most common string manipulating operations provided by the ECMAScript specification. The proposed analysis comes with a prototype static analyzer implementation for an imperative string manipulating language, allowing us to show and evaluate the improved precision of the proposed analysis.
A Hybrid Model to Simulate Test Cases of Electrical Power Systems
Authors: Rodriguez-Aguilar Roman
Published: May 2020

The development of solution algorithms for power system problems is based on hypothetical test systems and test cases. These systems are very scarce, and the degree of variability is relatively low. The constant development of the economic analysis in electrical power systems denotes the need to obtain standardized systems and cases. In this study, the creation of standardized test cases based on a hybrid model using Lévy alpha stable distributions and generalized additive models is proposed. The objective of the work is to present a methodological proposal for the creation of test environments for optimization models based on general information about the operation of particular power systems. The simulation of random values based on Lévy alpha stable distributions lets capturing the series impulsivity and demand peaks, and the use of generalized additive models permits capturing non-linearity in the behavior of the demand for electrical energy. The hybrid model will tolerate simulating as many instances as necessary, with a coherent behavior attached to the reality of the operation of the analyzed electrical systems.
Development of a Lightweight Prosthetic Hand for Patients with Amputated Fingers
Authors: Ryu Wooseok , Choi Youngjin , Choi Yong Je , Lee Sungon
Published: May 2020

Finger amputations are the most common upper limb amputation, and they occur approximately 100 times more often than hand amputations. We developed a prosthetic hand for amputees with a thumb and metacarpal. In this case of amputation, the installation of actuators and electrical components is difficult because space is considerably limited owing to the residual metacarpal. This design issue is solved by installing actuators vertically between finger modules and the mounting part where the electrical parts are embedded. With this design, the arrangement between the palm of the patient and the fingers of the prosthetic hand can be adjusted as well. Weight is also an especially important design issue in the development of a practical prosthetic hand because the patient perceives that weight. Most prosthetic hands are attached to the residual limb of the amputee by compressing the contact surface between the product and the amputated body part of the patient. Heavy weight causes users to feel discomfort and fatigue over extended periods of usage. In this study, all frames used in the proposed prosthetic hand were fabricated from nylon using multi-jet-fusion three-dimensional printing. As a result, the weight of the developed prosthetic hand was only 152.32 g but still had the desired strength and stiffness. Each prosthetic finger has four-degree-of-freedom. The distal interphalangeal, proximal interphalangeal, and metacarpophalangeal joints are coupled and driven by power from an actuator, which is transferred to each joint through the tendons. Adduction, abduction, and self-adaptive grasping motions were passively realized using linear and torsional springs. The prototype was fabricated based on these design concepts and functions, and its functionality was verified in experiments using diverse objects.
Estimation of Wind Turbine Angular Velocity Remotely Found on Video Mining and Convolutional Neural Network
Authors: Bahaghighat Mahdi , Xin Qin , Motamedi Seyed Ahmad , Zanjireh Morteza Mohammadi , Vacavant Antoine
Published: May 2020

Today, energy issues are more important than ever. Because of the importance of environmental concerns, clean and renewable energies such as wind power have been most welcomed globally, especially in developing countries. Worldwide development of these technologies leads to the use of intelligent systems for monitoring and maintenance purposes. Besides, deep learning as a new area of machine learning is sharply developing. Its strong performance in computer vision problems has conducted us to provide a high accuracy intelligent machine vision system based on deep learning to estimate the wind turbine angular velocity, remotely. This velocity along with other information such as pitch angle and yaw angle can be used to estimate the wind farm energy production. For this purpose, we have used SSD (Single Shot Multi-Box Detector) object detection algorithm and some specific classification methods based on DenseNet, SqueezeNet, ResNet50, and InceptionV3 models. The results indicate that the proposed system can estimate rotational speed with about 99.05 % accuracy.
Raman Spectral Analysis for Quality Determination of Grignard Reagent
Authors: Joshi Rahul , Joshi Ritu , Mo Changyeun , Faqeerzada Mohammad Akbar , Amanah Hanim Z. , Masithoh Rudiati Evi , Kim Moon S. , Cho Byoung-Kwan
Published: May 2020

Grignard reagent is one of the most popular materials in chemical and pharmaceutical reaction processes, and requires high quality with minimal adulteration. In this study, Raman spectroscopic technique was investigated for the rapid determination of toluene content, which is one of the common adulterants in Grignard reagent. Raman spectroscopy is the most suitable spectroscopic method to mitigate moisture and CO2 interference in the molecules of Grignard reagent. Raman spectra for the mixtures of toluene and Grignard reagent with different concentrations were analyzed with a partial least square regression (PLSR) method. The combination of spectral wavebands in the prediction model was optimized with a variables selection method of variable importance in projection (VIP). The results obtained from the VIP-based PLSR model showed the reliable performance of Raman spectroscopy for predicting the toluene concentration present in Grignard reagent with a correlation coefficient value of 0.97 and a standard error of prediction (SEP) of 0.71%. The results showed that Raman spectroscopy combined with multivariate analysis could be an effective analytical tool for rapid determination of the quality of Grignard reagent.
Air Pollution Sources’ Contribution to PM2.5 Concentration in the Northeastern Part of the Czech Republic
Authors: Seibert Radim , Nikolova Irina , Volná Vladimíra , Krejčí Blanka , Hladký Daniel
Published: May 2020

This article focuses on the source apportionment of air pollution in a specific northeastern part of the Czech Republic. The research area, located around the city of Třinec, is significantly affected by a complex spectrum of air pollution sources, including local residential heating (coal and wood burning), heavy industry (mainly iron and steel production), road traffic, and regional and long-range air pollution transport from the nearby cities, Poland, and other countries. The main pollution sources contributing to the total concentration of fine suspended particles (PM2.5) were evaluated on the basis of the measurements at three sites and on subsequent positive matrix factorization modeling. The six major air pollution factors were identified, and their relative and absolute contributions were quantified. The result of the study is that the most important current task of air protection is to reduce the residential emissions from solid fuels, which are responsible for approximately 50–60% of PM2.5 concentration, followed by the regional primary and secondary aerosol sources (up to 40% of the total PM2.5 aerosol mass). Lower contributions have been identified in the case of resuspended mineral and biogenic particles (15–20%), long-range (trans-European) air pollution transport (up to 10%), and heavy industry (up to 10% in the most affected location). A detailed discussion has been provided considering specific regional EC (elemental carbon)–OC (organic carbon) relations in the region with traditional coal-burning for household heating which complicate the interpretation of the PMF (Positive Matrix Factorization) results, especially due to the interference between the traffic, residential heating, and biogenic aerosol factors.
Microbial Community Composition Analysis in Spring Aerosols at Urban and Remote Sites over the Tibetan Plateau
Authors: Sharma Ghimire Prakriti , Kang Shichang , Sajjad Wasim , Ali Barkat , Tripathee Lekhendra , Chen Pengfei
Published: May 2020

This study presents features of airborne culturable bacteria and fungi from three different sites (Lanzhou; LZ; 1520 m ASL, Lhasa; LS; 3640 m ASL and Qomolangma; ZF; 4276 m ASL) representing urban (LZ and LS) and remote sites (ZF) over the Tibetan Plateau (TP). Total suspended particle (TSP) samples were collected with an air sampler (Laoying 2030, China) on a quartz filter. Community structures of bacteria and fungi were studied and compared among three different locations. The average levels of bacterial load in the outdoor air ranged from approximately 8.03 × 101 to 3.25 × 102 CFU m–3 (Colony forming unit per m3). However, the average levels of fungal loads ranged from approximately 3.88 × 100 to 1.55 × 101 CFU m−3. Bacterial load was one magnitude higher at urban sites LZ (2.06 × 102–3.25 × 102 CFU m−3) and LS (1.96 × 102–3.23 × 102 CFU m−3) compared to remote sites ZF (8.03 × 101–9.54 × 101 CFU m−3). Similarly, the maximum fungal load was observed in LZ (1.02 × 101–1.55 × 101 CFU m−3) followed by LS (1.03 × 101–1.49 × 101 CFU m−3) and ZF (3.88 × 100–6.26 × 100 CFU m−3). However, the maximum microbial concentration was observed on the same day of the month, corresponding to a high dust storm in Lanzhou during the sampling period. The reported isolates were identified by phylogenetic analysis of 16S rRNA genes for bacteria and ITS sequences for fungi amplified from directly extracted DNA. Bacterial isolates were mostly associated with Proteobacteria, Eurotiomycetes and Bacillus, whereas fungal isolates were mostly Aspergillus and Alternaria. Overall, this is a pioneer study that provides information about the airborne microbial concentration and composition of three sites over the TP region depending on environmental parameters. This study provided preliminary insight to carry out more advanced and targeted analyses of bioaerosol in the sites presented in the study.
On the Product Rule for the Hyperbolic Scator Algebra
Authors: Cieśliński Jan L. , Kobus Artur
Published: May 2020

Scator set, introduced by Fernández-Guasti and Zaldívar, is endowed with a very peculiar non-distributive product. In this paper we consider the scator space of dimension 1 + 2 and the so called fundamental embedding which maps the subset of scators with non-zero scalar component into 4-dimensional space endowed with a natural distributive product. The original definition of the scator product is induced in a straightforward way. Moreover, we propose an extension of the scator product on the whole scator space, including all scators with vanishing scalar component.
Aristotle’s Syllogistic as a Deductive System
Authors: Kulicki Piotr
Published: May 2020

Aristotle’s syllogistic is the first ever deductive system. After centuries, Aristotle’s ideas are still interesting for logicians who develop Aristotle’s work and draw inspiration from his results and even more from his methods. In the paper we discuss the essential elements of the Aristotelian system of syllogistic and Łukasiewicz’s reconstruction of it based on the tools of modern formal logic. We pay special attention to the notion of completeness of a deductive system as discussed by both authors. We describe in detail how completeness can be defined and proved with the use of an axiomatic refutation system. Finally, we apply this methodology to different axiomatizations of syllogistic presented by Łukasiewicz, Lemmon and Shepherdson.
Magnetotactic Bacteria and Magnetosomes as Smart Drug Delivery Systems: A New Weapon on the Battlefield with Cancer?
Authors: Kuzajewska Danuta , Wszołek Agata , Żwierełło Wojciech , Kirczuk Lucyna , Maruszewska Agnieszka
Published: May 2020

An important direction of research in increasing the effectiveness of cancer therapies is the design of effective drug distribution systems in the body. The development of the new strategies is primarily aimed at improving the stability of the drug after administration and increasing the precision of drug delivery to the destination. Due to the characteristic features of cancer cells, distributing chemotherapeutics exactly to the microenvironment of the tumor while sparing the healthy tissues is an important issue here. One of the promising solutions that would meet the above requirements is the use of Magnetotactic bacteria (MTBs) and their organelles, called magnetosomes (BMs). MTBs are commonly found in water reservoirs, and BMs that contain ferromagnetic crystals condition the magnetotaxis of these microorganisms. The presented work is a review of the current state of knowledge on the potential use of MTBs and BMs as nanocarriers in the therapy of cancer. The growing amount of literature data indicates that MTBs and BMs may be used as natural nanocarriers for chemotherapeutics, such as classic anti-cancer drugs, antibodies, vaccine DNA, and siRNA. Their use as transporters increases the stability of chemotherapeutics and allows the transfer of individual ligands or their combinations precisely to cancerous tumors, which, in turn, enables the drugs to reach molecular targets more effectively.
The Utility of Genomic and Transcriptomic Data in the Construction of Proxy Protein Sequence Databases for Unsequenced Tree Nuts
Authors: Pirone-Davies Cary , McFarland Melinda A. , Parker Christine H. , Adachi Yoko , Croley Timothy R.
Published: May 2020

As the apparent incidence of tree nut allergies rises, the development of MS methods that accurately identify tree nuts in food is critical. However, analyses are limited by few available tree nut protein sequences. We assess the utility of translated genomic and transcriptomic data for library construction with Juglans regia, walnut, as a model. Extracted walnuts were subjected to nano-liquid chromatography–mass spectrometry (n-LC-MS/MS), and spectra were searched against databases made from a six-frame translation of the genome (6FT), a transcriptome, and three proteomes. Searches against proteomic databases yielded a variable number of peptides (1156–1275), and only ten additional unique peptides were identified in the 6FT database. Searches against a transcriptomic database yielded results similar to those of the National Center for Biotechnology Information (NCBI) proteome (1200 and 1275 peptides, respectively). Performance of the transcriptomic database was improved via the adjustment of RNA-Seq read processing methods, which increased the number of identified peptides which align to seed allergen proteins by ~20%. Together, these findings establish a path towards the construction of robust proxy protein databases for tree nut species and other non-model organisms.
A Comparison between Several Response Surface Methodology Designs and a Neural Network Model to Optimise the Oxidation Conditions of a Lignocellulosic Blend
Authors: López Roberto , Fernández Camino , Pereira Fernando J. , Díez Ana , Cara Jorge , Martínez Olegario , Sánchez Marta E.
Published: May 2020

In this paper, response surface methodology (RSM) designs and an artificial neural network (ANN) are used to obtain the optimal conditions for the oxy-combustion of a corn–rape blend. The ignition temperature (Te) and burnout index (Df) were selected as the responses to be optimised, while the CO2/O2 molar ratio, the total flow, and the proportion of rape in the blend were chosen as the influencing factors. For the RSM designs, complete, Box–Behnken, and central composite designs were performed to assess the experimental results. By applying the RSM, it was found that the principal effects of the three factors were statistically significant to compute both responses. Only the interactions of the factors on Df were successfully described by the Box–Behnken model, while the complete design model was adequate to describe such interactions on both responses. The central composite design was found to be inadequate to describe the factor interactions. Nevertheless, the three methods predicted the optimal conditions properly, due to the cancellation of net positive and negative errors in the mathematical adjustment. The ANN presented the highest regression coefficient of all methods tested and needed only 20 experiments to reach the best predictions, compared with the 32 experiments needed by the best RSM method. Hence, the ANN was found to be the most efficient model, in terms of good prediction ability and a low resource requirement. Finally, the optimum point was found to be a CO2/O2 molar ratio of 3.3, a total flow of 108 mL/min, and 61% of rape in the biomass blend.
Radiosensitising Cancer Using Phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT) or Mammalian Target of Rapamycin (mTOR) Inhibitors
Authors: Wanigasooriya Kasun , Tyler Robert , Barros-Silva Joao D. , Sinha Yashashwi , Ismail Tariq , Beggs Andrew D.
Published: May 2020

Radiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients.
Targeting EpCAM by a Bispecific Trifunctional Antibody Exerts Profound Cytotoxic Efficacy in Germ Cell Tumor Cell Lines
Authors: Schönberger Stefan , Kraft Daniela , Nettersheim Daniel , Schorle Hubert , Casati Anna , Craveiro Rogerio B. , Mohseni Mahsa Mir , Calaminus Gabriele , Dilloo Dagmar
Published: May 2020

Outcome in high-risk patients with refractory or relapsed germ cell tumours (GCT) remains poor. Novel strategies enhancing therapeutic efficacy whilst limiting therapeutic burden are warranted, yet immunotherapy approaches geared towards activating endogenous antitumor responses have not been successful thus far. Redirection of cytotoxic effector cells by bispecific antibodies represents a promising approach in this setting. We demonstrate that the Epithelial Cell Adhesion Molecule (EpCAM) is broadly expressed in GCT cell lines of different histologic origin including seminoma, choriocarcinoma (CHC), and embryonal carcinoma (EC). In these GCT lines of variable EpCAM surface expression, targeting T cells by the prototypic bispecific EpCAM/CD3-antibody (bAb) Catumaxomab together with natural killer (NK) cell engagement via the Fc domain promotes profound cytotoxicity across a broad range of antibody dilutions. In contrast, tumor cell lysis mediated by either immune cell subset alone is influenced by surface density of the target antigen. In the CHC line JAR, NK cell-dependent cytotoxicity dominates, which may be attributed to differential surface expression of immunomodulatory proteins such as MHC-I, CD24, and Fas receptors on CHC and EC. In view of redirecting T cell therapy mediated by bispecific antibodies, such differences in GCT immunophenotype potentially favoring immune escape are worth further investigation.
Circulating MicroRNAs Regulating DNA Damage Response and Responsiveness to Cisplatin in the Prognosis of Patients with Non-Small Cell Lung Cancer Treated with First-Line Platinum Chemotherapy
Authors: Papadaki Chara , Monastirioti Alexia , Rounis Konstantinos , Makrakis Dimitrios , Kalbakis Konstantinos , Nikolaou Christoforos , Mavroudis Dimitrios , Agelaki Sofia
Published: May 2020

The expression of microRNA (miR)-21, miR-128, miR-155, and miR-181a involved in DNA damage response (DDR) and tumor responsiveness to platinum was assessed by RT-qPCR in the plasma of patients with non-small cell lung cancer (NSCLC; n = 128) obtained prior to initiation of first-line platinum chemotherapy. U6 small nuclear RNA (snRNA) was used for normalization, and fold change of each miRNA expression relative to the expression in healthy controls was calculated by the 2−ΔΔCt method. MicroRNA expression levels were correlated with patients’ outcomes. Integrated function and pathway enrichment analysis was performed to identify putative target genes. MiR-128, miR-155, and miR-181a expressions were higher in patients compared to healthy donors. MiRNA expression was not associated with response to treatment. High miR-128 and miR-155 were correlated with shorter overall survival (OS), whereas performance status (PS) 2 and high miR-128 independently predicted for decreased OS. In the squamous (SqCC) subgroup (n = 41), besides miR-128 and miR-155, high miR-21 and miR-181a expressions were also associated with worse survival and high miR-155 independently predicted for shorter OS. No associations of miRNA expression with clinical outcomes were observed in patients with non-SqCC (n = 87). Integrated function and pathway analysis on miRNA targets revealed significant enrichments in hypoxia-related pathways. Our study shows for the first time that plasma miR-128 and miR-155 hold independent prognostic implications in NSCLC patients treated with platinum-based chemotherapy possibly related to their involvement in tumor response to hypoxia. Further studies are needed to investigate the potential functional role of these miRNAs in an effort to exploit their therapeutic potential.
Fatty Acid Synthase Inhibitor G28 Shows Anticancer Activity in EGFR Tyrosine Kinase Inhibitor Resistant Lung Adenocarcinoma Models
Authors: Polonio-Alcalá Emma , Palomeras Sònia , Torres-Oteros Daniel , Relat Joana , Planas Marta , Feliu Lidia , Ciurana Joaquim , Ruiz-Martínez Santiago , Puig Teresa
Published: May 2020

Epidermal growth factor receptor (EGFR) tyrosine kinases inhibitors (TKIs) are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor an EGFR activating mutation. However, this treatment is not curative due to primary and secondary resistance such as T790M mutation in exon 20. Recently, activation of transducer and activator of transcription 3 (STAT3) in NSCLC appeared as an alternative resistance mechanism allowing cancer cells to elude the EGFR signaling. Overexpression of fatty acid synthase (FASN), a multifunctional enzyme essential for endogenous lipogenesis, has been related to resistance and the regulation of the EGFR/Jak2/STAT signaling pathways. Using EGFR mutated (EGFRm) NSCLC sensitive and EGFR TKIs’ resistant models (Gefitinib Resistant, GR) we studied the role of the natural polyphenolic anti-FASN compound (−)-epigallocatechin-3-gallate (EGCG), and its derivative G28 to overcome EGFR TKIs’ resistance. We show that G28’s cytotoxicity is independent of TKIs’ resistance mechanisms displaying synergistic effects in combination with gefitinib and osimertinib in the resistant T790M negative (T790M−) model and showing a reduction of activated EGFR and STAT3 in T790M positive (T790M+) models. Our results provide the bases for further investigation of G28 in combination with TKIs to overcome the EGFR TKI resistance in NSCLC.
Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome
Authors: Santonocito Concetta , Rizza Roberta , Paris Ida , De Marchis Laura , Paolillo Carmela , Tiberi Giordana , Scambia Giovanni , Capoluongo Ettore
Published: May 2020

Pathogenic variants (PVs) carriers in BRCA1 or BRCA2 are associated with an elevated lifetime risk of developing breast cancer (BC) and/or ovarian cancer (OC). The prevalence of BRCA1 and BRCA2 germline alterations is extremely variable among different ethnic groups. Particularly, the rate of variants in Italian BC and/or OC families is rather controversial and ranges from 8% to 37%, according to different reports. By In Vitro Diagnostic (IVD) next generation sequencing (NGS)-based pipelines, we routinely screened thousands of patients with either sporadic or cancer family history. By NGS, we identified new PVs and some variants of uncertain significance (VUS) which were also evaluated in silico using dedicated tools. We report in detail data regarding BRCA1/2 variants identified in 517 out of 2351 BC and OC patients. The aim of this study was to report the incidence and spectrum of BRCA1/2 variants observed in BC and/or OC patients, tested in at Policlinico Gemelli Foundation Hospital, the origin of which is mainly from Central and Southern Italy. This study provides an overview of the variant frequency in these geographic areas of Italy and provides data that could be used in the clinical management of patients.
Older Cancer Patients during the COVID-19 Epidemic: Practice Proposal of the International Geriatric Radiotherapy Group
Authors: Nguyen Nam P. , Vinh-Hung Vincent , Baumert Brigitta G. , Zamagni Alice , Arenas Meritxell , Motta Micaela , Lara Pedro Carlos , Myint Arthur Sun , Bonet Marta , Popescu Tiberiu , Vuong Te , Appalanaido Gokula Kumar , Trigo Lurdes , Karlsson Ulf , Thariat Juliette
Published: May 2020

The coronavirus disease 19 (COVID-19) pandemic is unprecedented as it reached all countries in the world within a record short period of time. Even though COVID-19 infection may be just severe in any adults, older adults (65-year-old or older) may experience a higher mortality rate. Among those affected, cancer patients may have a worse outcome compared to the general population because of their depressed immune status. As the health resources of most countries are limited, clinicians may face painful decisions about which patients to save if they require artificial ventilation. Cancer patients, especially the older ones, may be denied supportive care because of their shorter life expectancy. Thus, special considerations should be taken to prevent infection of older cancer patients and to provide them with adequate social support during their cancer treatment. The following proposal was reached: (1) Education of health care providers about the special needs of older cancer patients and their risks of infection. (2) Special consideration such as surgical masks and separate scheduling should be made to protect them from being infected. (3) Social services such as patient navigators should be provided to ensure adequate medical supply, food, and daily transportation to cancer centers. (4) Close monitoring through phone calls, telecommunication to ensure social distancing and psychological support from patient family to prevent anxiety and depression. (5) Shorter course of radiotherapy by use of hypofractionation where possible to decrease the needs for daily transportation and exposure to infection. (6) Enrollment of older cancer patients in clinical trials for potential antiviral medications if infection does occur. (7) Home health care telemedicine may be an effective strategy for older cancer patients with COVID-19 infection to avoid hospital admission when health care resources become restricted. (8) For selected patients, immunotherapy and targeted therapy may become the systemic therapy of choice for older cancer patients and need to be tested in clinical trials.
Thioholgamide A, a New Anti-Proliferative Anti-Tumor Agent, Modulates Macrophage Polarization and Metabolism
Authors: Dahlem Charlotte , Siow Wei Xiong , Lopatniuk Maria , Tse William K. F. , Kessler Sonja M. , Kirsch Susanne H. , Hoppstädter Jessica , Vollmar Angelika M. , Müller Rolf , Luzhetskyy Andriy , Bartel Karin , Kiemer Alexandra K.
Published: May 2020

Natural products represent powerful tools searching for novel anticancer drugs. Thioholgamide A (thioA) is a ribosomally synthesized and post-translationally modified peptide, which has been identified as a product of Streptomyces sp. MUSC 136T. In this study, we provide a comprehensive biological profile of thioA, elucidating its effects on different hallmarks of cancer in tumor cells as well as in macrophages as crucial players of the tumor microenvironment. In 2D and 3D in vitro cell culture models thioA showed potent anti-proliferative activities in cancer cells at nanomolar concentrations. Anti-proliferative actions were confirmed in vivo in zebrafish embryos. Cytotoxicity was only induced at several-fold higher concentrations, as assessed by live-cell microscopy and biochemical analyses. ThioA exhibited a potent modulation of cell metabolism by inhibiting oxidative phosphorylation, as determined in a live-cell metabolic assay platform. The metabolic modulation caused a repolarization of in vitro differentiated and polarized tumor-promoting human monocyte-derived macrophages: ThioA-treated macrophages showed an altered morphology and a modulated expression of genes and surface markers. Taken together, the metabolic regulator thioA revealed low activities in non-tumorigenic cells and an interesting anti-cancer profile by orchestrating different hallmarks of cancer, both in tumor cells as well as in macrophages as part of the tumor microenvironment.
Germline Mutation in MUS81 Resulting in Impaired Protein Stability is Associated with Familial Breast and Thyroid Cancer
Authors: Pinheiro Maisa , Lupinacci Fernanda Cristina Sulla , Santiago Karina Miranda , Drigo Sandra Aparecida , Marchi Fabio Albuquerque , Fonseca-Alves Carlos Eduardo , Andrade Sonia Cristina da Silva , Aagaard Mads Malik , Basso Tatiane Ramos , dos Reis Mariana Bisarro , Villacis Rolando André Rios , Roffé Martin , Hajj Glaucia Noeli Maroso , Jurisica Igor , Kowalski Luiz Paulo , Achatz Maria Isabel , Rogatto Silvia Regina
Published: May 2020

Multiple primary thyroid cancer (TC) and breast cancer (BC) are commonly diagnosed, and the lifetime risk for these cancers is increased in patients with a positive family history of both TC and BC. Although this phenotype is partially explained by TP53 or PTEN mutations, a significant number of patients are negative for these alterations. We judiciously recruited patients diagnosed with BC and/or TC having a family history of these tumors and assessed their whole-exome sequencing. After variant prioritization, we selected MUS81 c.1292G>A (p.R431H) for further investigation. This variant was genotyped in a healthy population and sporadic BC/TC tissues and investigated at the protein level and cellular models. MUS81 c.1292G>A was the most frequent variant (25%) and the strongest candidate due to its function of double-strand break repair. This variant was confirmed in four relatives from two families. MUS81 p.R431H protein exhibited lower expression levels in tumors from patients positive for the germline variant, compared with wild-type BC, and normal breast and thyroid tissues. Using cell line models, we showed that c.1292G>A induced protein instability and affected DNA damage response. We suggest that MUS81 is a novel candidate involved in familial BC/TC based on its low frequency in healthy individuals and proven effect in protein stability.
Venous Thromboembolism in Lymphoma: Risk Stratification and Antithrombotic Prophylaxis
Authors: Hohaus Stefan , Bartolomei Francesca , Cuccaro Annarosa , Maiolo Elena , Alma Eleonora , D’Alò Francesco , Bellesi Silvia , Rossi Elena , Stefano Valerio De
Published: May 2020

Lymphoma is listed among the neoplasias with a high risk of venous thromboembolism (VTE). Risk factors for VTE appear to differ from risk factors in solid tumors. We review the literature of the last 20 years for reports identifying these risk factors in cohorts consisting exclusively of lymphoma patients. We selected 25 publications. The most frequent studies were analyses of retrospective single-center cohorts. We also included two reports of pooled analyses of clinical trials, two meta-analyses, two analyses of patient registries, and three analyses of population-based databases. The VTE risk is the highest upfront during the first two months after lymphoma diagnosis and decreases over time. This upfront risk may be related to tumor burden and the start of chemotherapy as contributing factors. Factors consistently reported as VTE risk factors are aggressive histology, a performance status ECOG ≥ 2 leading to increased immobility, more extensive disease, and localization to particular sites, such as central nervous system (CNS) and mediastinal mass. Association between laboratory values that are part of risk assessment models in solid tumors and VTE risk in lymphomas are very inconsistent. Recently, VTE risk scores for lymphoma were developed that need further validation, before they can be used for risk stratification and primary prophylaxis. Knowledge of VTE risk factors in lymphomas may help in the evaluation of the individual risk-benefit ratio of prophylaxis and help to design prospective studies on primary prophylaxis in lymphoma.
Contrasting Effects of Potassium Addition on M3O4 (M = Co, Fe, and Mn) Oxides during Direct NO Decomposition Catalysis
Authors: Peck Torin C. , Roberts Charles A. , Reddy Gunugunuri K.
Published: May 2020

While the promotional effect of potassium on Co3O4 NO decomposition catalytic performance is established in the literature, it remains unknown if K is also a promoter of NO decomposition over similar simple first-row transition metal spinels like Mn3O4 and Fe3O4. Thus, potassium was impregnated (0.9–3.0 wt.%) on Co3O4, Mn3O4, and Fe3O4 and evaluated for NO decomposition reactivity from 400–650 °C. The activity of Co3O4 was strongly dependent on the amount of potassium present, with a maximum of ~0.18 [(µmol NO to N2) g−1 s−1] at 0.9 wt.% K. Without potassium, Fe3O4 exhibited deactivation with time-on-stream due to a non-catalytic chemical reaction with NO forming α-Fe2O3 (hematite), which is inactive for NO decomposition. Potassium addition led to some stabilization of Fe3O4, however, γ-Fe2O3 (maghemite) and a potassium–iron mixed oxide were also formed, and catalytic activity was only observed at 650 °C and was ~50× lower than 0.9 wt.% K on Co3O4. The addition of K to Mn3O4 led to formation of potassium–manganese mixed oxide phases, which became more prevalent after reaction and were nearly inactive for NO decomposition. Characterization of fresh and spent catalysts by scanning electron microscopy and energy dispersive X-ray analysis (SEM/EDX), in situ NO adsorption Fourier transform infrared spectroscopy, temperature programmed desorption techniques, X-ray powder diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) revealed the unique potassium promotion of Co3O4 for NO decomposition arises not only from modification of the interaction of the catalyst surface with NOx (increased potassium-nitrite formation), but also from an improved ability to desorb oxygen as product O2 while maintaining the integrity and purity of the spinel phase.
Synthesis and Evaluation of PtNi Electrocatalysts for CO and Methanol Oxidation in Low Temperature Fuel Cells
Authors: Caballero-Manrique Griselda , Garcia-Cardona Julia , Brillas Enric , Jaén Juan A. , Sánchez John Manuel , Cabot Pere L.
Published: May 2020

Pt(Ni)/C and PtRu(Ni)/C catalysts were synthesized by electroless deposition of Ni on a carbon dispersion followed by sequenced Pt deposition and spontaneous deposition of Ru species. The structural analyses of the catalysts with 88:12 and 98:2 Pt:Ni atomic ratios pointed out to the formation of small hexagonal Ni crystallites covered by thin cubic Pt surface structures with no evidence about PtNi alloy formation. The onset potentials for CO oxidation on Pt(Ni)/C and PtRu(Ni)/C were about 0.10 and 0.24 V more negative than those of Pt/C, thus indicating their better CO tolerance. The surface Ru species appeared to have the major effect by facilitating the CO removal by the bifunctional mechanism. The onset potential for the methanol oxidation reaction (MOR) of Pt(Ni)/C was about 0.15 V lower than that of Pt/C. The mass and specific activities together with the exchange current densities of the Pt(Ni)/C catalysts were also higher than those of Pt/C, making in evidence their higher activity in front of the MOR. The Tafel slopes for the MOR on Pt(Ni)/C suggested different reaction mechanism than on Pt/C. The electronic (ligand) effect of Ni on Pt was considered the main reason to explain the higher activity of Pt(Ni)/C in front of the CO oxidation and the MOR.