bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence-Based Prediction of Key Textural Properties from LUCAS and ICRAF Spectral Libraries
Authors: Gouda Mohamed Zakaria , Nagihi El Mehdi , Khiari Lotfi , Gallichand Jacques , Ismail Mahmoud
Published: August 2021

Soil texture is a key soil property influencing many agronomic practices including fertilization and liming. Therefore, an accurate estimation of soil texture is essential for adopting sustainable soil management practices. In this study, we used different machine learning algorithms trained on vis–NIR spectra from existing soil spectral libraries (ICRAF and LUCAS) to predict soil textural fractions (sand–silt–clay %). In addition, we predicted the soil textural groups (G1: Fine, G2: Medium, and G3: Coarse) using routine chemical characteristics as auxiliary. With the ICRAF dataset, multilayer perceptron resulted in good predictions for sand and clay (R2 = 0.78 and 0.85, respectively) and categorical boosting outperformed the other algorithms (random forest, extreme gradient boosting, linear regression) for silt prediction (R2 = 0.81). For the LUCAS dataset, categorical boosting consistently showed a high performance for sand, silt, and clay predictions (R2 = 0.79, 0.76, and 0.85, respectively). Furthermore, the soil texture groups (G1, G2, and G3) were classified using the light gradient boosted machine algorithm with a high accuracy (83% and 84% for ICRAF and LUCAS, respectively). These results, using spectral data, are very promising for rapid diagnosis of soil texture and group in order to adjust agricultural practices.
Age-Related Individual Behavioural Characteristics of Adult Wistar Rats
Authors: Sudakov Sergey K. , Alekseeva Elena V. , Nazarova Galina A. , Bashkatova Valentina G.
Published: August 2021

The aim of this work was to study age-related changes in the behaviour of adult Wistar rats using the open field (OF) and elevated plus maze (EPM) tests. Behavioural changes related to motor activity and anxiety were of particular interest. Results showed that as male and female rats progressed from 2 to 5 months of age, there was a decrease in the level of motor and exploratory activities and an increase in their level of anxiety. Age-related changes were dependent upon initial individual characteristics of behaviour. For example, animals that demonstrated high motor activity at 2 months become significantly less active by 5 months, and animals that showed a low level of anxiety at 2 months become more anxious by 5 months. Low-activity and high-anxiety rats did not show any significant age-related changes in OF and EPM tests from 2 to 5 months of age, except for a decrease in the number of rearings in the EPM. Thus, the behaviour of the same adult rat at 2 and 5 months of age is significantly different, which may lead to differences in the experimental results of physiological and pharmacological studies using adult animals of different ages.
Some Genetic and Environmental Effects on Equine Asthma in Polish Konik Horses
Authors: Borowska Alicja , Wolska Daria , Niedzwiedz Artur , Borowicz Hieronim , Jaworski Zbigniew , Siemieniuch Marta , Szwaczkowski Tomasz
Published: August 2021

Current knowledge of the genetic and environmental backgrounds of equine asthma seems to be insufficient, especially for primitive horse breeds. The main objectives of this study were to estimate the effects of sex, birth period, stud, parentage line and inbreeding on asthma morbidity in Polish Konik horses. Records of 274 horses (housed in two studs) were analysed. These animals were allocated to maternal and paternal lines. Individual inbreeding coefficients were extracted from the additive relationship matrix. Horses underwent diagnosis based on observation of the basic symptoms (high frequency of coughing and excessive nasal discharge). Subsequently, some horses (28 individuals) were clinically examined to confirm the earlier observations. Generally, no significant effects of parentage line on heaves morbidity were identified by the use of logistic regression, although the Pearson’s chi-squared test had shown that individuals of some maternal and paternal lines had a predisposition to severe equine asthma. It was concluded that the individual inbreeding level is not associated with the incidence of EA, but a significant effect of the maternal inbreeding coefficient may be observed. It was also found that there is some variability in the incidence of this disease between studs.
A Retrospective Study on Bacteriology, Clinicopathologic and Radiographic Features in 28 Cats Diagnosed with Pyothorax
Authors: Sim Juin Jia , Lau Seng Fong , Omar Sharina , Watanabe Malaika , Aslam Muhammad Waseem
Published: August 2021

This retrospective study aimed to determine the etiological, clinicopathological, and radiographic features and outcome of feline pyothorax cases. Medical records from twenty-eight cats with pyothorax aged from 4 months to 10 years (median 10 months) diagnosed between 2013 and 2020 were reviewed. Dyspnoea (75.0%), abnormal lung sounds (75.0%) and open-mouth breathing (64.3%) were the predominant respiratory signs. Leucocytosis (61.5%), particularly monocytosis (68.0%), and hyperglobulinaemia (65.4%) were among the most prominent findings in blood analysis. Bilateral pleural effusion was found in 67.9% of the thoracic radiographs. A total of 47.4% of the cytological samples revealed the presence of bacteria, while all had positive bacterial growth. Pasteurella multocida, E. coli, Streptococcus spp., and Staphylococcus spp. were the predominant aerobic bacteria isolated from pleural effusion samples. A chest tube was placed in 64.3% of the cats and 66.7% of cats with chest tubes survived. In total, 46.4% of cats with pyothorax recovered. Amoxicillin–clavulanate was the antimicrobial of choice against aerobic bacteria found in this study and should be given in combination with antimicrobials that cover anaerobic bacteria. Chest tube placement is crucial for treatment success. Cytological results and bacterial culture may not be consistent; thus, bacterial culture should be performed for every case.
Estimation of Rice Biomass at Different Growth Stages by Using Fractal Dimension in Image Processing
Authors: Hu Yijun , Shen Jingfang , Qi Yonghao
Published: August 2021

Rice has long served as the staple food in Asia, and the cultivation of high-yield rice crops draws increasing attention from academic researchers. The prediction of rice growth condition by image features realizes nondestructive prediction and it has great implications for smart agriculture. We found a special image parameter called the fractal dimension that can improve the effect of the prediction model. As an important geometric feature, the fractal dimension could be calculated from the image, but it is rarely used in the field of rice growth prediction. In this paper, we attempt to combine the fractal dimension with traditional rice image features to improve the effect of the model. The thresholding method is used to transform the cropped rice image into binary image, and the box-counting method is used to calculate the fractal dimension of the image. The correlation coefficients are calculated to select the characteristics with a strong correlation with biomass. The prediction models of dry weight, fresh weight and plant height of rice are established by using random forest, support vector regression and linear regression. By evaluating the prediction effect of the model, it can be concluded that the fractal dimension can improve the prediction effect of the model. Among the models obtained by the three methods, the multiple linear regression model has the best comprehensive effect, with the dry weight prediction model R2 reaching 0.8697, the fresh weight prediction model R2 reaching 0.8631 and the plant height prediction model R2 reaching 0.9196. The model established in this paper has a fine effect and has a certain guiding significance in rice research.
Three-Dimensional Broadband and Isotropic Double-Mesh Twin-Wire Media for Meta-Lenses
Authors: Wang Hairu , Chen Qiao , Zetterstrom Oskar , Quevedo-Teruel Oscar
Published: August 2021

Lenses are used for multiple applications, including communications, surveillance and security, and medical instruments. In homogeneous lenses, the contour is used to control the electromagnetic propagation. Differently, graded-index lenses make use of inhomogeneous materials, which is an extra degree of freedom. This extra degree of freedom enables the design of devices with a high performance. For instance, rotationally symmetric lenses without spherical aberrations, e.g., the Luneburg lens, can be designed. However, the manufacturing of such lenses is more complex. One possible approach to implement these lenses is using metamaterials, which are able to produce equivalent refractive indices. Here, we propose a new type of three-dimensional metamaterial formed with two independent sets of wires. The double-mesh twin-wire structure permits the propagation of a first mode without cut-off frequency and with low dispersion and high isotropy. These properties are similar to periodic structures with higher symmetries, such as glide symmetry. The variations of the equivalent refractive index are achieved with the dimension of the meandered wires. The potential of this new metamaterial is demonstrated with simulated results of a Luneburg meta-lens.
Determination and Quantification of Heavy Metals in Sediments through Laser-Induced Breakdown Spectroscopy and Partial Least Squares Regression
Authors: Yoon Sangmi , Choi Jaeseung , Moon Seung-Jae , Choi Jung Hyun
Published: August 2021

Conventional analysis techniques and sample preprocessing methods for identifying trace metals in soil and sediment samples are costly and time-consuming. This study investigated the determination and quantification of heavy metals in sediments by using a Laser-Induced Breakdown Spectroscopy (LIBS) system and multivariate chemometric analysis. Principle Component Analysis (PCA) was conducted on the LIBS spectra at the emission lines of 11 selected elements (Al, Ca, Cd, Cr, Fe, K, Mg, Na, Ni, Pb, and Si). The results showed apparent clustering of four types of sediment samples, suggesting the possibility of application of the LIBS technique for distinguishing different types of sediments. Mainly, the Cd, Cr, and Pb concentrations in the sediments were analyzed. A data-smoothing method—namely, the Savitzky–Golay (SG) derivative—was used to enhance the performance of the Partial Least Squares Regression (PLSR) model. The performance of the PLSR model was evaluated in terms of the coefficient of determination (R2), Root Mean Square Error of Calibration (RMSEC), and Root Mean Square Error of Cross Validation (RMSECV). The results obtained using the PLSR with the SG derivative were improved in terms of the R2 and RMSECV, except for Cr. In particular, the results for Cd obtained with the SG derivative showed a decrease of 25% in the RMSECV value. This demonstrated that the PLSR model with the SG derivative is suitable for the quantitative analysis of metal components in sediment samples and can play a significant role in controlling and managing the water quality of rivers.
Virtual and Physical Prototyping of Reconfigurable Parallel Mechanisms with Single Actuation
Authors: Fomin Alexey , Petelin Daniil , Antonov Anton , Glazunov Victor , Ceccarelli Marco
Published: August 2021

The paper presents novel models of reconfigurable parallel mechanisms (RPMs) with a single active degree-of-freedom (1-DOF). The mechanisms contain three to six identical kinematic chains, which provide three (for the tripod) to zero (for the hexapod) uncontrollable DOFs. Screw theory is applied to carry out mobility analysis and proves the existence of controllable and uncontrollable DOFs of these mechanisms. Each kinematic chain in the synthesized mechanisms consists of planar and spatial parts. Such a design provides them with reconfiguration capabilities even when the driving link is fixed. This allows reproduction of diverse output trajectories without using additional actuators. In this paper, the model of a mechanism with six kinematic chains (hexapod) has been virtually and physically prototyped. The designing and assembling algorithms are developed using the detailed computer-aided design (CAD) model, which was further used to carry out kinetostatic analysis considering complex geometry of mechanism elements and friction among all contacting surfaces of joints. The developed virtual prototype and its calculation data have been further applied to fabricate mechanism elements and assemble an actuated full-scale physical prototype for future testing.
Lightweight Blockchain Processing. Case Study: Scanned Document Tracking on Tezos Blockchain
Authors: Allouche Mohamed , Frikha Tarek , Mitrea Mihai , Memmi Gérard , Chaabane Faten
Published: August 2021

To bridge the current gap between the Blockchain expectancies and their intensive computation constraints, the present paper advances a lightweight processing solution, based on a load-balancing architecture, compatible with the lightweight/embedding processing paradigms. In this way, the execution of complex operations is securely delegated to an off-chain general-purpose computing machine while the intimate Blockchain operations are kept on-chain. The illustrations correspond to an on-chain Tezos configuration and to a multiprocessor ARM embedded platform (integrated into a Raspberry Pi). The performances are assessed in terms of security, execution time, and CPU consumption when achieving a visual document fingerprint task. It is thus demonstrated that the advanced solution makes it possible for a computing intensive application to be deployed under severely constrained computation and memory resources, as set by a Raspberry Pi 3. The experimental results show that up to nine Tezos nodes can be deployed on a single Raspberry Pi 3 and that the limitation is not derived from the memory but from the computation resources. The execution time with a limited number of fingerprints is 40% higher than using a classical PC solution (value computed with 95% relative error lower than 5%).
Integer Search Algorithm: A New Discrete Multi-Objective Algorithm for Pavement Maintenance Management Optimization
Authors: Alqaili Abdulraaof , Qais Mohammed , Al-Mansour Abdullah
Published: August 2021

Optimization techniques keep road performance at a good level using a cost-effective maintenance strategy. Thus, the trade-off between cost and road performance is a multi-objective function. This paper offers a new multi-objective stochastic algorithm for discrete variables, which is called the integer search algorithm (ISA). This algorithm is applied to an optimal pavement maintenance management system (PMMS), where the variables are discrete. The PMMS optimization can be achieved by maximizing the condition of pavement with a minimum cost at specified constraints, so the PMMS is a constrained multi-objective problem. The ISA and genetic algorithm (GA) are applied to improve the performance condition rating (PCR) of the pavement in developing countries, where the annual budget is limited, so a minimum cost for three years’ maintenance is scheduled. Study results revealed that the ISA produced an optimal solution for multi-function objectives better than the optimal solution of GA.
A Novel Robust Classification Method for Ground-Based Clouds
Authors: Yu Aihua , Tang Ming , Li Gang , Hou Beiping , Xuan Zhongwei , Zhu Bihong , Chen Tianliang
Published: August 2021

Though the traditional convolutional neural network has a high recognition rate in cloud classification, it has poor robustness in cloud classification with occlusion. In this paper, we propose a novel scheme for cloud classification, in which the convolutional neural networks are used for feature extraction and a weighted sparse representation coding is adopted for classification. Three such algorithms are proposed. Experiments are carried out using the multimodal ground-based cloud dataset and the results show that in the case of occlusion, the accuracy of the proposed methods can be much improved over the traditional convolutional neural network-based algorithms.
High Sensitivity Multi-Axes Rotation Sensing Using Large Momentum Transfer Point Source Atom Interferometry
Authors: Li Jinyang , R. M. da Silva Gregório , Huang Wayne C. , Fouda Mohamed , Bonacum Jason , Kovachy Timothy , Shahriar Selim M.
Published: August 2021

A point source interferometer (PSI) is a device where atoms are split and recombined by applying a temporal sequence of Raman pulses during the expansion of a cloud of cold atoms behaving approximately as a point source. The PSI can work as a sensitive multi-axes gyroscope that can automatically filter out the signal from accelerations. The phase shift arising from the rotations is proportional to the momentum transferred to each atom from the Raman pulses. Therefore, by increasing the momentum transfer, it should be possible to enhance the sensitivity of the PSI. Here, we investigate the degree of enhancement in sensitivity that could be achieved by augmenting the PSI with large momentum transfer (LMT) employing a sequence of many Raman pulses with alternating directions. We analyze how factors such as Doppler detuning, spontaneous emission, and the finite initial size of the atomic cloud compromise the advantage of LMT and how to find the optimal momentum transfer under these limitations, with both the semi-classical model and a model under which the motion of the center of mass of each atom is described quantum mechanically. We identify a set of realistic parameters for which LMT can improve the PSI by a factor of nearly 40.
Combined Strategies to Prompt the Biological Reduction of Chlorinated Aliphatic Hydrocarbons: New Sustainable Options for Bioremediation Application
Authors: Rossi Marta M. , Dell’Armi Edoardo , Lorini Laura , Amanat Neda , Zeppilli Marco , Villano Marianna , Petrangeli Papini Marco
Published: August 2021

Groundwater remediation is one of the main objectives to minimize environmental impacts and health risks. Chlorinated aliphatic hydrocarbons contamination is prevalent and presents particularly challenging scenarios to manage with a single strategy. Different technologies can manage contamination sources and plumes, although they are usually energy-intensive processes. Interesting alternatives involve in-situ bioremediation strategies, which allow the chlorinated contaminant to be converted into non-toxic compounds by indigenous microbial activity. Despite several advantages offered by the bioremediation approaches, some limitations, like the relatively low reaction rates and the difficulty in the management and control of the microbial activity, can affect the effectiveness of a bioremediation approach. However, those issues can be addressed through coupling different strategies to increase the efficiency of the bioremediation strategy. This mini review describes different strategies to induce the reduction dechlorination reaction by the utilization of innovative strategies, which include the increase or the reduction of contaminant mobility as well as the use of innovative strategies of the reductive power supply. Subsequently, three future approaches for a greener and more sustainable intervention are proposed. In particular, two bio-based materials from renewable resources are intended as alternative, long-lasting electron-donor sources (e.g., polyhydroxyalkanoates from mixed microbial cultures) and a low-cost adsorbent (e.g., biochar from bio-waste). Finally, attention is drawn to novel bio-electrochemical systems that use electric current to stimulate biological reactions.
Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein
Authors: Nevinsky Georgy A. , Baranova Svetlana V. , Buneva Valentina N. , Dmitrenok Pavel S.
Published: August 2021

Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well.
Aldosterone Excess Induced Mitochondria Decrease and Dysfunction via Mineralocorticoid Receptor and Oxidative Stress In Vitro and In Vivo
Authors: Tsai Cheng-Hsuan , Pan Chien-Ting , Chang Yi-Yao , Peng Shih-Yuan , Lee Po-Chin , Liao Che-Wei , Shun Chia-Tung , Li Po-Ting , Wu Vin-Cent , Chou Chia-Hung , Tsai I-Jung , Hung Chi-Sheng , Lin Yen-Hung
Published: August 2021

Aldosterone excess plays a major role in the progression of cardiac dysfunction and remodeling in clinical diseases such as primary aldosteronism and heart failure. However, the effect of aldosterone excess on cardiac mitochondria is unclear. In this study, we investigated the effect of aldosterone excess on cardiac mitochondrial dysfunction and its mechanisms in vitro and in vivo. We used H9c2 cardiomyocytes to investigate the effect and mechanism of aldosterone excess on cardiac mitochondria, and further investigated them in an aldosterone-infused ICR mice model. The results of the cell study showed that aldosterone excess decreased mitochondrial DNA, COX IV and SOD2 protein expressions, and mitochondria ATP production. These effects were abolished or attenuated by treatment with a mineralocorticoid receptor (MR) antagonist and antioxidant. With regard to the signal transduction pathway, aldosterone suppressed cardiac mitochondria through an MR/MAPK/p38/reactive oxygen species pathway. In the mouse model, aldosterone infusion decreased the amount of cardiac mitochondrial DNA and COX IV protein, and the effects were also attenuated by treatment with an MR antagonist and antioxidant. In conclusion, aldosterone excess induced a decrease in mitochondria and mitochondrial dysfunction via MRs and oxidative stress in vitro and in vivo.
Enhanced Biomechanically Mediated “Phagocytosis” in Detached Tumor Cells
Authors: Goldstein Yoel , Tischenko Katerina , Brill-Karniely Yifat , Benny Ofra
Published: August 2021

Uptake of particles by cells involves various natural mechanisms that are essential for their biological functions. The same mechanisms are used in the engulfment of synthetic colloidal drug carriers, while the extent of the uptake affects the biological performance and selectivity. Thus far, little is known regarding the effect of external biomechanical stimuli on the capacity of the cells to uptake nano and micro carriers. This is relevant for anchorage-dependent cells that have detached from surfaces or for cells that travel in the body such as tumor cells, immune cells and various circulating stem cells. In this study, we hypothesize that cellular deformability is a crucial physical effector for the successful execution of the phagocytosis-like uptake in cancer cells. To test this assumption, we develop a well-controlled tunable method to compare the uptake of inert particles by cancer cells in adherent and non-adherent conditions. We introduce a self-designed 3D-printed apparatus, which enables constant stirring while facilitating a floating environment for cell incubation. We reveal a mechanically mediated phagocytosis-like behavior in various cancer cells, that was dramatically enhance in the detached cell state. Our findings emphasize the importance of including proper biomechanical cues to reliably mimic certain physiological scenarios. Beyond that, we offer a cost-effective accessible research tool to study mixed cultures for both adherent and non-adherent cells.
Dramatic Course of Paediatric Cryptogenic Febrile Infection-Related Epilepsy Syndrome with Unusual Chronic Phase Presentation—A Case Report with Literature Study
Authors: Rachfalska Natalia , Pietruszewski Jerzy , Paprocka Justyna
Published: August 2021

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic, extremely rare epileptic encephalopathy. It strikes previously healthy school-aged children and is usually cryptogenic. Its dramatic onset with refractory status epilepticus is always preceded by a nonspecific febrile illness. The seizure activity in FIRES may last for several weeks with little to no response to antiepileptic treatment, usually resulting in the usage of anaesthetics. This acute phase is followed by a chronic, refractory epilepsy and cognitive deficit, that persist for the rest of the patient’s life. Still to this day no definite cause has been described. In this study we review the current finding in FIRES and describe a case of a 4-year-old patient with a dramatic course of the acute phase in FIRES and unusual presentation of the chronic phase, which is dominated by extrapyramidal symptoms such as dystonia. This case highlights that the clinical presentation of FIRES may differ from those frequently described in literature.
Prognostic Discrimination of Alternative Lymph Node Classification Systems for Patients with Radically Resected Non-Metastatic Colorectal Cancer: A Cohort Study from a Single Tertiary Referral Center
Authors: Prassas Dimitrios , Verde Pablo Emilio , Pavljak Carlo , Rehders Alexander , Krieg Sarah , Luedde Tom , Knoefel Wolfram Trudo , Krieg Andreas
Published: August 2021

Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients with Stage III radically resected CRC.
Clinicobiological Characteristics and Outcomes of Patients with T-Cell Large Granular Lymphocytic Leukemia and Chronic Lymphoproliferative Disorder of Natural Killer Cells from a Single Institution
Authors: Rivero Andrea , Mozas Pablo , Jiménez Laura , López-Guerra Mónica , Colomer Dolors , Bataller Alex , Correa Juan , Rivas-Delgado Alfredo , Bastidas Gabriela , Baumann Tycho , Martínez-Trillos Alejandra , Delgado Julio , Giné Eva , Campo Elías , López-Guillermo Armando , Villamor Neus , Magnano Laura , Matutes Estella
Published: August 2021

T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorder of natural killer (NK) cells are two infrequent diseases characterized by clonal expansions of cytotoxic T lymphocytes and NK cells, respectively. Somatic mutations of STAT3 are involved in the pathogenesis of these entities. We describe the clinicobiological features, mutational status of STAT3/STAT5B, treatment and outcome of 131 patients. Neutropenia was the most frequent finding at diagnosis, followed by anemia. Concurrent hematological disorders were diagnosed in 37% of patients and autoimmune conditions and solid tumors in 17% and 15%, respectively. All patients who needed treatment belonged to the CD8+CD57+ group. Remarkably, patients included in the CD4+ group had a higher association with solid tumors (p = 0.037). STAT3 mutations were found in 17% of patients, mainly Y640F and D661Y mutations. Patients carrying STAT3 mutations more frequently presented with anemia, neutropenia, high LDH, high large granular lymphocyte counts and need for treatment (p = 0.0037). Methotrexate was the most frequently used agent (72% of cases). The overall response rate to all treatments was 50%. The 10-year overall survival of this series was 78%, with no differences according to the mutational status of STAT3. We compared the survival of these patients with the general Spanish population and no differences were found, confirming the indolent nature of these hematological malignancies. Our study further extends findings documented by others on the clinical behavior of the disease and the impact of STAT3, and for the first time analyzes survival compared to a matched general Spanish population.
Irreversible Electroporation and Nivolumab Combined with Intratumoral Administration of a Toll-Like Receptor Ligand, as a Means of In Vivo Vaccination for Metastatic Pancreatic Ductal Adenocarcinoma (PANFIRE-III). A Phase-I Study Protocol
Authors: Geboers Bart , Timmer Florentine , Ruarus Alette , Pouw Johanna , Schouten Evelien , Bakker Joyce , Puijk Robbert , Nieuwenhuizen Sanne , Dijkstra Madelon , van den Tol M. , de Vries Jan , Oprea-Lager Daniela , Menke-van der Houven van Oordt C. , van der Vliet Hans , Wilmink Johanna , Scheffer Hester , de Gruijl Tanja , Meijerink Martijn ,   on behalf of the Dutch Pancreatic Cancer Group
Published: August 2021

Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor’s immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO-2125 (a toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO-2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT), 18F-FDG and 18F-BMS-986192 (PD-L1) positron emission tomography (PET)-CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti-tumor response, it may ultimately improve PDAC’s dismal prognosis.
Evaluation of Colon-Specific Plasma Nanovesicles as New Markers of Colorectal Cancer
Authors: Nazarova Inga , Slyusarenko Maria , Sidina Elena , Nikiforova Nadezhda , Semiglazov Vladislav , Semiglazova Tatiana , Aigner Achim , Rybakov Evgeny , Malek Anastasia
Published: August 2021

Purpose: Developing new and efficient approaches for the early diagnosis of colorectal cancer (CRC) is an important issue. Circulating extracellular nanovesicles (ENVs) present a promising class of cancer markers. Cells of well-differentiated adenocarcinomas retain the molecular characteristics of colon epithelial cells, and the ENVs secreted by these cells may have colon-specific surface markers. We hypothesize that an increase in the number of ENVs carrying colon-specific markers could serve as a diagnostic criterion for colorectal cancer. Experimental design: Potential colon-specific markers were selected based on tissue-specific expression profile and cell surface membrane localization data. Plasma was collected from CRC patients (n = 48) and healthy donors (n = 50). The total population of ENVs was isolated with a two-phase polymer system. ENVs derived from colon epithelium cells were isolated using immune-beads with antibodies to colon-specific markers prior to labelling with antibodies against exosomal tetraspanins (CD63 and CD9) and quantification by flow cytometry. Results: The number of ENVs positive for single colon cancer markers was found to be significantly higher in the plasma of CRC patients compared with healthy donors. The efficacy of detection depends on the method of ENV labelling. The diagnostic efficacy was estimated by ROC analysis (the AUC varied between 0.71 and 0.79). The multiplexed isolation of colon-derived ENVs using immune-beads decorated with antibodies against five markers allowed for a further increase in the diagnostic potency of the method (AUC = 0.82). Conclusions: ENVs derived from colon epithelium may serve as markers of differentiated CRC (adenocarcinomas). The composition of ligands used for capturing colon-derived ENVs and their method of labelling are critical for the efficacy of this proposed diagnostic approach.
Inhibitors Targeting CDK9 Show High Efficacy against Osimertinib and AMG510 Resistant Lung Adenocarcinoma Cells
Authors: Padmanabhan Jaya , Saha Biswarup , Powell Chase , Mo Qianxing , Perez Bradford A. , Chellappan Srikumar
Published: August 2021

Non-small cell lung cancer has a 5-year survival rate of less than 12–15%, calling for the development of additional therapeutic strategies to combat this disease. Here we tested the efficacy of inhibiting cyclin-dependent kinase 9 (CDK9) on lung cancer cell lines with K-Ras and EGFR mutations and on lung cancer organoids. Three different CDK9 inhibitors reduced the viability and anchorage-independent growth of lung cancer cell lines at very low nanomolar to micromolar concentrations. CDK9 inhibition suppressed the expression of the anti-apoptotic protein, Mcl1, as well as the embryonic stem cell transcription factors, Sox2 and Sox9, which are pro-tumorigenic. In contrast, treatment with CDK9 inhibitors increased the levels of WT p53 and its downstream target p21 in K-Ras mutant cell lines. Furthermore, the CDK9 inhibitors could markedly reduce the viability of Osimertinib-resistant PC9 and AMG510-resistant H23 and H358 cells with comparable efficacy as the parental cells. CDK9 inhibitors could also significantly reduce the growth and viability of lung cancer organoids with high potency. Taken together, the data presented here strongly suggest that CDK9 inhibitors would be efficacious against K-Ras mutant and EGFR mutant NSCLCs, including those that develop resistance to targeted therapies.
Distinct Molecular Mechanisms of Altered HLA Class II Expression in Malignant Melanoma
Authors: Meyer Stefanie , Handke Diana , Mueller Anja , Biehl Katharina , Kreuz Markus , Bukur Jürgen , Koehl Ulrike , Lazaridou Maria-Filothei , Berneburg Mark , Steven André , Massa Chiara , Seliger Barbara
Published: August 2021

Background: The human leukocyte antigen (HLA) class II molecules are constitutively expressed in some melanoma, but the underlying molecular mechanisms have not yet been characterized. Methods: The expression of HLA class II antigen processing machinery (APM) components was determined in melanoma samples by qPCR, Western blot, flow cytometry and immunohistochemistry. Immunohistochemical and TCGA datasets were used for correlation of HLA class II expression to tumor grading, T-cell infiltration and patients’ survival. Results: The heterogeneous HLA class II expression in melanoma samples allowed us to characterize four distinct phenotypes. Phenotype I totally lacks constitutive HLA class II surface expression, which is inducible by interferon-gamma (IFN-γ); phenotype II expresses low basal surface HLA class II that is further upregulated by IFN-γ; phenotype III lacks constitutive and IFN-γ controlled HLA class II expression, but could be induced by epigenetic drugs; and in phenotype IV, lack of HLA class II expression is not recovered by any drug tested. High levels of HLA class II APM component expression were associated with an increased intra-tumoral CD4+ T-cell density and increased patients’ survival. Conclusions: The heterogeneous basal expression of HLA class II antigens and/or APM components in melanoma cells is caused by distinct molecular mechanisms and has clinical relevance.
MicroRNA and Other Non-Coding RNAs in Epstein–Barr Virus-Associated Cancers
Authors: Notarte Kin Israel , Senanayake Suranga , Macaranas Imee , Albano Pia Marie , Mundo Lucia , Fennell Eanna , Leoncini Lorenzo , Murray Paul
Published: August 2021

EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs.
Radiation-Associated Angiosarcoma of the Breast and Chest Wall Treated with Thermography-Controlled, Contactless wIRA-Hyperthermia and Hypofractionated Re-Irradiation
Authors: Notter Markus , Stutz Emanuel , Thomsen Andreas R. , Vaupel Peter
Published: August 2021

Background: Radiation-associated angiosarcoma of the breast (RAASB) is a rare, challenging disease, with surgery being the accepted basic therapeutic approach. In contrast, the role of adjuvant and systemic therapies is a subject of some controversy. Local recurrence rates reported in the literature are mostly heterogeneous and are highly dependent on the extent of surgery. In cases of locally recurrent or unresectable RAASB, prognosis is very poor. Methods: We retrospectively report on 10 consecutive RAASB patients, most of them presenting with locally recurrent or unresectable RAASB, which were treated with thermography-controlled water-filtered infrared-A (wIRA) superficial hyperthermia (HT) immediately followed by re-irradiation (re-RT). Patients with RAASB were graded based on their tumor extent before onset of radiotherapy (RT). Results: We recorded a local control (LC) rate dependent on tumor extent ranging from a high LC rate of 100% (two of two patients) in the adjuvant setting with an R0 or R2 resection to a limited LC rate of 33% (one of three patients) in patients with inoperable, macroscopic tumor lesions. Conclusion: Combined HT and re-RT should be considered as an option (a) for adjuvant treatment of RAASB, especially in cases with positive resection margins and after surgery of local recurrence (LR), and (b) for definitive treatment of unresectable RAASB.
Effect of Scalp Cooling on the Pharmacokinetics of Paclitaxel
Authors: van Doorn Leni , van Rosmalen Mandy M. , van der Deure Wendy M. , Oomen-de Hoop Esther , Porrazzo Robert , Wijngaard Sophie M. , Boere Ingrid A. , Veenstra Paola , Ibrahim Eman , de Bruijn Peter , Friberg Lena E. , Koolen Stijn L. W. , Mathijssen Ron H. J. , Jager Agnes
Published: August 2021

Chemotherapy-induced alopecia (CIA), a side effect with high impact, can be prevented by cooling the scalp during the administration of some cytotoxic drugs. However, the effects of this prolonged scalp cooling on the pharmacokinetics of chemotherapy have never been investigated. In this study, we compared the pharmacokinetics of the widely used chemotherapeutic agent paclitaxel (weekly dose of 80–100 mg/m2) in female patients with solid tumors using concomitant scalp cooling (n = 14) or not (n = 24). Blood samples were collected in all patients for pharmacokinetic analyses up to 6 h after one course of paclitaxel administration. The primary endpoint was the clearance (L/h) of paclitaxel. Paclitaxel clearance—expressed as relative difference in geometric means—was 6.8% (90% CI: −16.7% to 4.4%) lower when paclitaxel was administered with concomitant scalp cooling versus paclitaxel infusions without scalp cooling. Within the subgroup of patients using scalp cooling, paclitaxel clearance was not statistically significantly different between patients with CIA (alopecia grade 1 or 2) and those without CIA. Hence, scalp cooling did not negatively influence the clearance of paclitaxel treatment.
Visualization of Commercial Coating Penetration into Fagus crenata Blume Wood Using a Non-Destructive X-ray Microtomography
Authors: Ekaputri Tyana Solichah , Apsari Ayuni Nur , Tanaka Takashi
Published: August 2021

Coatings can be used as a preservative method to protect the wood, especially the wood surface. The different component of the coating’s dependence of the purpose of it. The Japanese beech (Fagus crenata Blume) applied by several Japanese commercials coating materials. The coatings application used were spray type and brush type. X-ray microtomography in Fuji, Japan was used for visualized the coating samples. The X-ray target used were Cu, and Mo with Al filter. The X-ray image analysis in 2D and 3D were conducted using image J and VGStudio Max, respectfully. The coating’s containing materials and the concentration of it strongly affected the image result of X-ray microtomography visualization. The different X-ray target shows the different image results. The larger energy of X-ray (Mo with Al filter) is recommended to use for visualization. The X-ray images shows the penetration phenomena, which can be applied to calculate the penetration depth.
Ganxiao Dong: A Hotspot of Cave Biodiversity in Northern Guangxi, China
Authors: Huang Sunbin , Wei Guofu , Wang Hengsong , Liu Weixin , Bedos Anne , Deharveng Louis , Tian Mingyi
Published: August 2021

Located in the core zone of Mulun National Nature Reserve in northern Guangxi, the limestone cave Ganxiao Dong harbours the richest cave fauna currently known in China. In total, 26 species of cave invertebrates have been recognized so far, in spite of limited sampling efforts. Of them, 20 are troglobionts or stygobionts, including one snail, four millipedes, three spiders, one harvestman, three isopods, two springtails, two crickets, one non-glowing sticky worm, and three trechine beetles. Six other species are troglophiles. The most remarkable characteristic of this fauna is its high number of troglomorphic species, especially among millipedes, crickets and beetles.
How Can We Record Reliable Information on Animal Colouration in the Wild?
Authors: Lunghi Enrico , Bacci Francesco , Zhao Yahui
Published: August 2021

Animal colouration is a phenotypic trait that can provide important information on species ecology and adaptation. Describing animal colours can be very challenging, and digital images may help in this difficult task. Obtaining an image with colours similar to those observed in nature is not trivial, as many factors can alter the final result. Some studies highlighted the importance of a proper post-production and analysis of the images to obtain the best results, but unfortunately very little attention has been paid to how to obtain standardised images suitable to be employed in zoological and ecological studies. This study aims to give evidence about the importance of shooting pictures in standardised condition to obtain reliable data on animal colourations. We provide a method that allows to obtain standardised pictures with colours that are comparable to those observed on wild animals. We used a method that creates an in situ standardised environment to shoot photos of relatively small animals. Our method allows to fully control lights, the factor that affect pictures the most. We also provided a test on the efficiency of this method. Using a colour checker card as reference, we compared the divergence of the Red-Green-Blue channel values obtained from pictures shot in complete darkness with those read by a colorimeter. The average divergence in RGB values between the colorimeter and the RAW images was about 4%. This divergence increased when light disturbance occurred. Our method highlighted the importance of the moment in which pictures are taken, and demonstrated that a fully controlled method is essential for obtaining reliable information on animal colourations, data that can be employed in ecological and evolutionary studies.
Teacher Education during the COVID-19 Lockdown: Insights from a Formative Intervention Approach Involving Online Feedback
Authors: Pereira Íris Susana Pires , Fernandes Eva Lopes , Flores Maria Assunção
Published: August 2021

This paper examines preservice teachers’ perspectives on assessment feedback developed in a teacher education course during the first lockdown due to the COVID-19 pandemic. As initially negotiated with students, feedback was learner-centred and involved a formative intervention approach applied iteratively by the teacher educator over the course of one semester. Although such feedback was initially face-to-face, it had to be given exclusively online following the unexpected closure of the university. Analysis of student teachers’ perspectives, which were collected through an online questionnaire completed after their final assessment, reveals both positive and critical aspects regarding the feedback provided by the teacher educator. While reaffirming the significance of feedback as a crucial element for learning in online teacher education contexts, the findings also show that the clarity, affective bonding and multimodal meaning-making involved in face-to-face interaction are particularly challenging when the communication of feedback is digitally mediated. The implications and limitations of such findings are discussed.