bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Label Feature Selection Based on High-Order Label Correlation Assumption
Authors: Zhang Ping , Gao Wanfu , Hu Juncheng , Li Yonghao
Published: July 2020

Multi-label data often involve features with high dimensionality and complicated label correlations, resulting in a great challenge for multi-label learning. Feature selection plays an important role in multi-label learning to address multi-label data. Exploring label correlations is crucial for multi-label feature selection. Previous information-theoretical-based methods employ the strategy of cumulative summation approximation to evaluate candidate features, which merely considers low-order label correlations. In fact, there exist high-order label correlations in label set, labels naturally cluster into several groups, similar labels intend to cluster into the same group, different labels belong to different groups. However, the strategy of cumulative summation approximation tends to select the features related to the groups containing more labels while ignoring the classification information of groups containing less labels. Therefore, many features related to similar labels are selected, which leads to poor classification performance. To this end, Max-Correlation term considering high-order label correlations is proposed. Additionally, we combine the Max-Correlation term with feature redundancy term to ensure that selected features are relevant to different label groups. Finally, a new method named Multi-label Feature Selection considering Max-Correlation (MCMFS) is proposed. Experimental results demonstrate the classification superiority of MCMFS in comparison to eight state-of-the-art multi-label feature selection methods.
Automated Data Acquisition System Using a Neural Network for Prediction Response in a Mode-Locked Fiber Laser
Authors: Martinez-Angulo Jose Ramon , Perez-Careta Eduardo , Hernandez-Garcia Juan Carlos , Marquez-Figueroa Sandra , Barron Zambrano Jose Hugo , Jauregui-Vazquez Daniel , Filoteo-Razo Jose David , Lauterio-Cruz Jesus Pablo , Pottiez Olivier , Estudillo-Ayala Julian Moises , Rojas-Laguna Roberto
Published: July 2020

In this paper, we proposed a system to integrate optical and electronic instrumentation devices to predict a mode-locking fiber laser response, using a remote data acquisition with processing through an artificial neural network (ANN). The system is made up of an optical spectrum analyzer (OSA), oscilloscope (OSC), polarimeter (PAX), and the data acquisition automation through transmission control protocol/internet protocol (TCP/IP). A graphic user interface (GUI) was developed for automated data acquisition with the purpose to study the operational characteristics and stability at the passively mode-locked fiber laser (figure-eight laser, F8L) output. Moreover, the evolution of the polarization state and the behavior of the pulses are analyzed when polarization is changed by proper control plate adjustments. The data is processed using deep learning techniques, which provide the characteristics of the pulse at the output. Therefore, the parameter classification-identification is in accordance with the input polarization tilt used for the laser optimization.
Pre-Selection of the Optimal Sitting of Phase-Shifting Transformers Based on an Optimization Problem Solved within a Coordinated Cross-Border Congestion Management Process
Authors: Urresti-Padrón Endika , Jakubek Marcin , Jaworski Wojciech , Kłos Michał
Published: July 2020

The current European policy roadmap aims at forcing the TSOs to coordinate remedial actions used for relieving the congestions in the synchronous power system. In this paper, an optimization problem for coordinated congestion management is described and its results obtained for a real European use cases created in the H2020 EU-SysFlex project are presented. First of all, these results prove the feasibility of a central optimization problem for the coordination of the cross-border congestion management process. Next, the formulated optimization problem is used to tackle the issue of planning the investments in phase-shifting transformers (PSTs), for the purpose of increasing the efficiency/decreasing the cost of congestion management. Finally, this paper introduces two optimization-based indicators for pre-selecting the investment sites, which may be used to support the decision makers aiming at decreasing the costs of coordinated congestion management.
Least Squares Method for Identification of IGBT Thermal Impedance Networks Using Direct Temperature Measurements
Authors: Njawah Achiri Humphrey Mokom , Smidl Vaclav , Peroutka Zdenek , Streit Lubos
Published: July 2020

State-of-the-art methods for determining thermal impedance networks for IGBT (Insulated Gate Bipolar Transistor) modules usually involves the establishment of the relationship between the measured transistor or diode voltage and temperature under homogenous temperature distribution across the IGBT module. The junction temperature is recomputed from the established voltage–temperature relationship and used in determining the thermal impedance network. This method requires accurate measurement of voltage drop across the transistors and diodes under specific designed heating and cooling profiles. Validation of the junction temperature is usually done using infrared camera or sensors placed close to the transistors or diodes (in some cases and open IGBT module) so that the measured temperature is as close to the junction as possible. In this paper, we propose an alternative method for determining the IGBT thermal impedance network using the principles of least squares. This method uses measured temperatures for defined heating and cooling cycles under different cooling conditions to determine the thermal impedance network. The results from the proposed method are compared with those obtained using state-of-the-art methods.
Automated Data Filtering Approach for ANN Modeling of Distributed Energy Systems: Exploring the Application of Machine Learning
Authors: Nikpey Somehsaraei Homam , Ghosh Susmita , Maity Sayantan , Pramanik Payel , De Sudipta , Assadi Mohsen
Published: July 2020

To realize the distributed generation and to make the partnership between the dispatchable units and variable renewable resources work efficiently, accurate and flexible monitoring needs to be implemented. Due to digital transformation in the energy industry, a large amount of data is and will be captured every day, but the inability to process them in real time challenges the conventional monitoring and maintenance practices. Access to automated and reliable data-filtering tools seems to be crucial for the monitoring of many distributed generation units, avoiding false warnings and improving the reliability. This study aims to evaluate a machine-learning-based methodology for autodetecting outliers from real data, exploring an interdisciplinary solution to replace the conventional manual approach that was very time-consuming and error-prone. The raw data used in this study was collected from experiments on a 100-kW micro gas turbine test rig in Norway. The proposed method uses Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to detect and filter out the outliers. The filtered datasets are used to develop artificial neural networks (ANNs) as a baseline to predict the normal performance of the system for monitoring applications. Results show that the filtering method presented is reliable and fast, minimizing time and resources for data processing. It was also shown that the proposed method has the potential to enhance the performance of the predictive models and ANN-based monitoring.
Exergetic Evaluation of an Ethylene Refrigeration Cycle
Authors: Amaral Francisco , Santos Alex , Calixto Ewerton , Pessoa Fernando , Santana Delano
Published: July 2020

The production of light olefins by selective steam cracking is an energy-intensive process, and ethylene and propylene refrigeration cycles are key parts of it. The objective of this study was to identify opportunities for energy savings in an ethylene refrigeration cycle through an exergetic analysis. Two main causes of lower operational efficiency were identified: (1) Lower polytropic efficiency of the refrigerant compressor and (2) operating with the compressor mini-flow valve open to ensure reliability. The evaluation showed that the amount of irreversibilities generated by the cycle in operation is 22% higher than that predicted by the original design, which represents a 14% lower exergy efficiency. There is a potential savings of 0.20 MW in the cycle’s energy consumption with the implementation of the following improvements: recover refrigerant compressor efficiency by performing maintenance on the equipment and optimize the flow distribution between the recycle valve, the level control valve, and the temperature control valve.
Optimal Chiller Loading for Energy Conservation Using an Improved Fruit Fly Optimization Algorithm
Authors: Qi Min-Yong , Li Jun-Qing , Han Yu-Yan , Dong Jin-Xin
Published: July 2020

In the multi-chiller of the air conditioning system, the optimal chiller loading (OCL) is an important research topic. This research is to find the appropriate partial load ratio (PLR) for each chiller in order to minimize the total energy consumption of the multi-chiller under the system cooling load (CL) requirements. However, this optimization problem has not been well studied. In this paper, in order to solve the OCL problem, we propose an improved fruit fly optimization algorithm (IFOA). A linear generation mechanism is developed to uniformly generate candidate solutions, and a new dynamic search radius method is employed to balance the local and global search ability of IFOA. To empirically evaluate the performance of the proposed IFOA, a number of comparative experiments are conducted on three well-known cases. The experimental results show that IFOA found 14 optimal values (the optimal values among all algorithms) under a total of 17 CLs in three cases, and the ratio of the optimal values found was 82.4%, which was the highest among all algorithms. In addition, the mean value of all objective functions of IFOA is smaller and the standard deviation is equal to or close to 0, which proves that the algorithm has high stability. It can be concluded that IFOA is an ideal method to solve the OCL problem.
Mathematical Description of the Groundwater Flow and that of the Impurity Spread, which Use Temporal Caputo or Riemann–Liouville Fractional Partial Derivatives, Is Non-Objective
Authors: Balint Agneta M. , Balint Stefan
Published: July 2020

In this paper, it is shown that the mathematical description of the bulk fluid flow and that of content impurity spread, which uses temporal Caputo or temporal Riemann–Liouville fractional order partial derivatives, having integral representation on a finite interval, in the case of a horizontal unconfined aquifer is non-objective. The basic idea is that different observers using this type of description obtain different results which cannot be reconciled, in other words, transformed into each other using only formulas that link the numbers representing a moment in time for two different choices from the origin of time measurement. This is not an academic curiosity; it is rather a problem to find which one of the obtained results is correct.
Deciphering the Impact of a Bacterial Infection on Meiotic Recombination in Arabidopsis with Fluorescence Tagged Lines
Authors: Gratias Ariane , Geffroy Valérie
Published: July 2020

Plants are under strong evolutionary pressure to maintain surveillance against pathogens. One major disease resistance mechanism is based on NB-LRR (NLR) proteins that specifically recognize pathogen effectors. The cluster organization of the NLR gene family could favor sequence exchange between NLR genes via recombination, favoring their evolutionary dynamics. Increasing data, based on progeny analysis, suggest the existence of a link between the perception of biotic stress and the production of genetic diversity in the offspring. This could be driven by an increased rate of meiotic recombination in infected plants, but this has never been strictly demonstrated. In order to test if pathogen infection can increase DNA recombination in pollen meiotic cells, we infected Arabidopsis Fluorescent Tagged Lines (FTL) with the virulent bacteria Pseudomonas syringae. We measured the meiotic recombination rate in two regions of chromosome 5, containing or not an NLR gene cluster. In all tested intervals, no significant difference in genetic recombination frequency between infected and control plants was observed. Although it has been reported that pathogen exposure can sometimes increase the frequency of recombinant progeny in plants, our findings suggest that meiotic recombination rate in Arabidopsis may be resilient to at least some pathogen attack. Alternative mechanisms are discussed.
Sociocultural Influences, Drive for Thinness, Drive for Muscularity, and Body Dissatisfaction among Korean Undergraduates
Authors: You Sukkyung , Shin Kyulee
Published: July 2020

For many years, body dissatisfaction was considered a western phenomenon, and was studied mostly in Caucasian women. Recent studies, however, suggest that these issues are also present in men and in other ethnic groups. This research investigated the differential effects of various sociocultural pressures transmitted from the media, one’s parents, and one’s peers on the drives for thinness and muscularity, and body dissatisfaction among 1125 Korean college students (56% male) using structural equation modeling. The results indicate that, after controlling for body mass index and exercise, media pressures exerted the largest effects on participants’ body ideals and, in turn, body dissatisfaction across both genders (β = 0.44, and 0.30, p < 0.05, for females and males, respectively). This study’s results also indicate that there are considerable gender differences in this relationship. Specifically, the results show that parental and media pressure had significant indirect relationships with body dissatisfaction via the drive for thinness among females, while peer and media pressures had significant indirect relationships with body dissatisfaction via the drive for muscularity among males. As body dissatisfaction is known to significantly affect an individual’s mental and physical health, future research needs to identify relevant influential factors in this area, as well as the paths they have leading to increased body dissatisfaction.
Correlation and Reliability Analyses among the Upper Cervical Rotation-Flexion Test, Upper Cervical Flexion-Extension Test, and Upper Cervical Flexion Angle Measurement Using Radiography
Authors: Do KwangSun , Choi JaeSung , Kim JaeEun , Yim JongEun
Published: July 2020

(1) Background: The cervical rotation-flexion test is one method of measuring the range of motion of the upper cervical spine; however, this test has not been investigated in detail. The aim of this study was to investigate the reliability and concurrent validity of the upper cervical rotation-flexion test. (2) Methods: Twenty-five healthy individuals (13 women and 12 men) participated in this study. The participants underwent radiography, the upper cervical flexion-extension test, and the upper cervical rotation-flexion test in a sitting position while wearing a cervical goniometer to measure the upper cervical flexion angle. Three experienced physical therapists administered the upper cervical rotation-flexion test using the cervical device, twice for each participant. Inter-rater and intra-rater reliabilities were evaluated using the intraclass correlation coefficient (95% confidence interval). (3) Results: The inter-rater and intra-rater reliability values of the total scores were excellent. The results of the upper cervical rotation-flexion test significantly correlated with those of the radiographic evaluation of the upper cervical flexion angle (r = 0.80, p < 0.001) and those of the upper cervical flexion-extension test (r = 0.77, p < 0.001). Significant correlations among the three test results were observed. (4) Conclusions: The findings of this study suggest that the upper cervical rotation-flexion test is meaningful for independently measuring the upper cervical flexion angle.
Who Is Afraid of Population Aging? Myths, Challenges and an Open Question from the Civil Economy Perspective
Authors: Calvo-Sotomayor Iñigo , Atutxa Ekhi , Aguado Ricardo
Published: July 2020

Population aging is a great human achievement, but the economic literature normally addresses its effects in a narrow way and as a “problem” to be solved. The objective of this paper is to provide a more balanced approach to aging by calling into question some widespread ideas in the economic literature on aging, such as its supposed negative influence on economic growth, its impact on labor productivity or the assumption that aging societies are incapable of applying reforms. The paper adopts the renewed civil economy framework and takes as a reference the existing literature about beliefs and wrong assumptions on aging. The innovative contribution of this analysis lies in its effort to foster a positive perspective in the population aging field of research and in challenging negative associations regarding old-age stereotypes.
A Fish Leukocyte Immune-Type Receptor Uses a Novel Intracytoplasmic Tail Networking Mechanism to Cross-Inhibit the Phagocytic Response
Authors: Fei Chenjie , Zwozdesky Myron A. , Stafford James L.
Published: July 2020

Channel catfish (Ictalurus punctatus) leukocyte immune-type receptors (IpLITRs) are a family of immunoregulatory proteins shown to regulate several innate immune cell effector responses, including phagocytosis. The precise mechanisms of IpLITR-mediated regulation of the phagocytic process are not entirely understood, but we have previously shown that different IpLITR-types use classical as well as novel pathways for controlling immune cell-mediated target engulfment. To date, all functional assessments of IpLITR-mediated regulatory actions have focused on the independent characterization of select IpLITR-types in transfected cells. As members of the immunoglobulin superfamily, many IpLITRs share similar extracellular Ig-like domains, thus it is possible that various IpLITR actions are influenced by cross-talk mechanisms between different IpLITR-types; analogous to the paired innate receptor paradigm in mammals. Here, we describe in detail the co-expression of different IpLITR-types in the human embryonic AD293 cell line and examination of their receptor cross-talk mechanisms during the regulation of the phagocytic response using imaging flow cytometry, confocal microscopy, and immunoprecipitation protocols. Overall, our data provides interesting new insights into the integrated control of phagocytosis via the antagonistic networking of independent IpLITR-types that requires the selective recruitment of inhibitory signaling molecules for the initiation and sustained cross-inhibition of phagocytosis.
Endosomal-Lysosomal Processing of Neurodegeneration-Associated Proteins in Astrocytes
Authors: Wong Ching-On
Published: July 2020

Most common neurodegenerative diseases (NDs) are characterized by deposition of protein aggregates that are resulted from misfolding, dysregulated trafficking, and compromised proteolytic degradation. These proteins exert cellular toxicity to a broad range of brain cells and are found in both neurons and glia. Extracellular monomeric and oligomeric ND-associated proteins are taken up by astrocytes, the most abundant glial cell in the brain. Internalization, intracellular trafficking, processing, and disposal of these proteins are executed by the endosomal-lysosomal system of astrocytes. Endosomal-lysosomal organelles thus mediate the cellular impact and metabolic fate of these toxic protein species. Given the indispensable role of astrocytes in brain metabolic homeostasis, the endosomal-lysosomal processing of these proteins plays a fundamental role in altering the trajectory of neurodegeneration. This review aims at summarizing the mounting evidence that has established the essential role of astrocytic endosomal-lysosomal organelles in the processing of amyloid precursor proteins, Apolipoprotein E (ApoE), tau, alpha synuclein, and huntingtin, which are associated with NDs such as Alzheimer’s, Parkinson’s, and Huntington diseases.
The Role of miR-375-3p and miR-200b-3p in Gastrointestinal Stromal Tumors
Authors: Gyvyte Ugne , Lukosevicius Rokas , Inciuraite Ruta , Streleckiene Greta , Gudoityte Greta , Bekampyte Justina , Valentini Serena , Salteniene Violeta , Ruzgys Paulius , Satkauskas Saulius , Zviniene Kristina , Kupcinskas Juozas , Skieceviciene Jurgita
Published: July 2020

Deregulated microRNA (miRNA) expression profiles and their contribution to carcinogenesis have been observed in virtually all types of human cancer. However, their role in the pathogenesis of rare mesenchymal gastrointestinal stromal tumors (GISTs) is not well defined, yet. In this study, we aimed to investigate the role of two miRNAs strongly downregulated in GIST—miR-375-3p and miR-200b-3p—in the pathogenesis of GIST. To achieve this, miRNA mimics were transfected into GIST-T1 cells and changes in the potential target gene mRNA and protein expression, as well as alterations in cell viability, migration, apoptotic cell counts and direct miRNA–target interaction, were evaluated. Results revealed that overexpression of miR-375-3p downregulated the expression of KIT mRNA and protein by direct binding to KIT 3′UTR, reduced GIST cell viability and migration rates. MiR-200b-3p lowered expression of ETV1 protein, directly targeted and lowered expression of EGFR mRNA and protein, and negatively affected cell migration rates. To conclude, the present study identified that miR-375-3p and miR-200b-3p have a tumor-suppressive role in GIST.
A Comprehensive Mapping of the Druggable Cavities within the SARS-CoV-2 Therapeutically Relevant Proteins by Combining Pocket and Docking Searches as Implemented in Pockets 2.0
Authors: Gervasoni Silvia , Vistoli Giulio , Talarico Carmine , Manelfi Candida , Beccari Andrea R. , Studer Gabriel , Tauriello Gerardo , Waterhouse Andrew Mark , Schwede Torsten , Pedretti Alessandro
Published: July 2020

(1) Background: Virtual screening studies on the therapeutically relevant proteins of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) require a detailed characterization of their druggable binding sites, and, more generally, a convenient pocket mapping represents a key step for structure-based in silico studies; (2) Methods: Along with a careful literature search on SARS-CoV-2 protein targets, the study presents a novel strategy for pocket mapping based on the combination of pocket (as performed by the well-known FPocket tool) and docking searches (as performed by PLANTS or AutoDock/Vina engines); such an approach is implemented by the Pockets 2.0 plug-in for the VEGA ZZ suite of programs; (3) Results: The literature analysis allowed the identification of 16 promising binding cavities within the SARS-CoV-2 proteins and the here proposed approach was able to recognize them showing performances clearly better than those reached by the sole pocket detection; and (4) Conclusions: Even though the presented strategy should require more extended validations, this proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which are clearly amenable for virtual screening campaigns and drug repurposing studies. All results generated by the study and the Pockets 2.0 plug-in are available for download.
Rapid Regulation of Human Multidrug and Extrusion Transporters hMATE1 and hMATE2K
Authors: Kantauskaitė Marta , Hucke Anna , Reike Moritz , Ahmed Eltayeb Sara , Xiao Chuyan , Barz Vivien , Ciarimboli Giuliano
Published: July 2020

Vectorial transport of organic cations (OCs) in renal proximal tubules is mediated by sequential action of human OC transporter 2 (hOCT2) and human multidrug and toxic extrusion protein 1 and 2K (hMATE1 and hMATE2K), expressed in the basolateral (hOCT2) and luminal (hMATE1 and hMATE2K) plasma membranes, respectively. It is well known that hOCT2 activity is subjected to rapid regulation by several signaling pathways, suggesting that renal OC secretion may be acutely adapted to physiological requirements. Therefore, in this work, the acute regulation of hMATEs stably expressed in human embryonic kidney cells was characterized using the fluorescent substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) as a marker. A specific regulation of ASP+ transport by hMATE1 and hMATE2K measured in uptake and efflux configurations was observed. In the example of hMATE1 efflux reduction by inhibition of casein kinase II, it was also shown that this regulation is able to modify transcellular transport of ASP+ in Madin–Darby canine kidney II cells expressing hOCT2 and hMATE1 on the basolateral and apical membrane domains, respectively. The activity of hMATEs can be rapidly regulated by some intracellular pathways, which sometimes are common to those found for hOCTs. Interference with these pathways may be important to regulate renal secretion of OCs.
Parity Attenuates Intraepithelial Corneal Sensory Nerve Loss in Female Mice
Authors: Stepp Mary Ann , Pal-Ghosh Sonali , Tadvalkar Gauri , de Paiva Cintia S.
Published: July 2020

Aging impacts the ocular surface and reduces intraepithelial corneal nerve (ICN) density in male and female mice. Many researchers use retired breeders to study naturally aged female mice. Yet, the impact of parity and the length of time since breeders were retired on age-related changes in the intraepithelial corneal nerves is not known. Here we study 2 month (M) nulliparous (NP) females as well as 9M, 10M, and 11M NP and multiparous (MP) female mice to determine whether parity impacts the age-related decline seen in corneal axon density; 9M male mice are also included in these assessments. After showing that parity attenuates age-related loss in axon density, we also assess the impact of parity on corneal epithelial cell proliferation and find that it impacts cell proliferation and axon density normalized by cell proliferation. Stromal nerve arborization is also impacted by aging with parity enhancing stromal nerves in older mice. qPCR was performed on 20 genes implicated in ICN density using corneal epithelial RNA isolated from 10M NP and MP mice and showed that NGF expression was significantly elevated in MP corneal epithelium. Corneal sensitivity was significantly higher in 9M MP mice compared to NP mice and increased sensitivity in MP mice was accompanied by increased nerve terminals in the apical and middle cell layers. Together, these data show that parity in mice attenuates several aspects of the age-related decline seen on the ocular surface by retaining sensory axons and corneal sensitivity as mice age.
Synthesis, Properties, and Biological Applications of Metallic Alloy Nanoparticles
Authors: Huynh Kim-Hung , Pham Xuan-Hung , Kim Jaehi , Lee Sang Hun , Chang Hyejin , Rho Won-Yeop , Jun Bong-Hyun
Published: July 2020

Metallic alloy nanoparticles are synthesized by combining two or more different metals. Bimetallic or trimetallic nanoparticles are considered more effective than monometallic nanoparticles because of their synergistic characteristics. In this review, we outline the structure, synthesis method, properties, and biological applications of metallic alloy nanoparticles based on their plasmonic, catalytic, and magnetic characteristics.
Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy
Authors: Puntigam Lisa K. , Jeske Sandra S. , Götz Marlies , Greiner Jochen , Laban Simon , Theodoraki Marie-Nicole , Doescher Johannes , Weissinger Stephanie E. , Brunner Cornelia , Hoffmann Thomas K. , Schuler Patrick J.
Published: July 2020

Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy.
Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development
Authors: Telegina Darya V. , Kulikova Elizabeth A. , Kozhevnikova Oyuna S. , Kulikov Alexander V. , Khomenko Tatyana M. , Volcho Konstantin P. , Salakhutdinov Nariman F. , Kolosova Nataliya G.
Published: July 2020

Tyrosine phosphatase STEP (striatal-enriched tyrosine protein phosphatase) is a brain-specific protein phosphatase and is involved in the pathogenesis of many neurodegenerative diseases. Here, we examined the impact of STEP on the development of age-related macular degeneration (AMD)-like pathology in senescence-accelerated OXYS rats. Using OXYS and Wistar rats (control), we for the first time demonstrated age-dependent changes in Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the retina. The increases in STEP protein levels and the decrease of total and STEP phosphatase activities in the retina (as compared with Wistar rats) preceded the manifestation of clinical signs of AMD in OXYS rats (age 20 days). There were no differences in these retinal parameters between 13-month-old Wistar rats and OXYS rats with pronounced signs of AMD. Inhibition of STEP with TC-2153 during progressive AMD-like retinopathy (from 9 to 13 months of age) reduced the thickness of the retinal inner nuclear layer, as evidenced by a decreased amount of parvalbumin-positive amacrine neurons. Prolonged treatment with TC-2153 had no effect on Ptpn5 mRNA expression, STEP46 and STEP61 protein levels, and their phosphatase activity in the OXYS retina. Thus, TC-2153 may negatively affect the retina through mechanisms unrelated to STEP.
The Use of Bovine Xenogeneic Bone Graft for Dega Pelvic Osteotomy in Children with Hip Dysplasia: A Retrospective Study of 147 Treated Hips
Authors: Stiel Norbert , Moritz Menard , Babin Kornelia , Suling Anna , Rupprecht Martin , Beil Frank T. , Stuecker Ralf , Spiro Alexander S.
Published: July 2020

Backgrounds: Dega pelvic osteotomy is commonly used to correct acetabular dysplasia in children with open triradiate cartilage. The use of bovine xenogeneic bone graft (Tutobone®) for Dega osteotomy has not been reported so far. This study aimed to determine the clinical and radiological outcome in a large series of children with hip dysplasia who were treated by Dega osteotomy using a bovine xenogeneic block for stabilisation. Methods: A retrospective, single-centre study was conducted including 101 patients (147 hips) with different underlying diseases. The acetabular angle of Hilgenreiner (AA) and the lateral center-edge angle (LCA) were analysed to quantify the correction of acetabular indices. Graft incorporation was assessed using the Goldberg scoring system. Results: the mean preoperative AA improved from 28.1 (SD: 6.7) to 14.7 (SD: 5.1) after surgery (p < 0.001). The mean preoperative LCA improved from 9.9 (SD: 6.7) to 21.8 (SD: 6.8) postoperatively (p < 0.001). Both indices remained stable at the one-year follow-up examination. Graft incorporation was excellent with a mean Goldberg score of 6.6. Heterotopic ossification occurred in one hip without clinical relevance. Graft-related complications were not noted. Conclusions: Dega osteotomy using Tutobone® is safe and effective in the treatment of acetabular dysplasia in children independent of the underlying disease.
Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events
Authors: Gyselaers Wilfried
Published: July 2020

This review integrates the currently available information on the molecular, cellular, and systemic mechanisms involved in the pathophysiology of preeclampsia. It highlights that the growth, protection, and promotion of the conceptus requires the modulation of an intact maternal immune system, communication between the mother and fetus, and adaptation of the maternal organic functions. A malfunction in any of these factors, on either side, will result in a failure of the cascade of events required for the normal course of pregnancy. Maladaptive processes, initially aiming to protect the conceptus, fail to anticipate the gradually increasing cardiovascular volume load during the course of pregnancy. As a result, multiple organ dysfunctions install progressively and eventually reach a state where mother and/or fetus are at risk of severe morbidity or even mortality, and where the termination of pregnancy becomes the least harmful solution. The helicopter view on pathophysiologic processes associated with preeclampsia, as presented in this paper, illustrates that the etiology of preeclampsia cannot be reduced to one single mechanism, but is to be considered a cascade of consecutive events, fundamentally not unique to pregnancy.
Vaginal Progesterone Has No Diabetogenic Potential in Twin Pregnancies: A Retrospective Case-Control Study on 1686 Pregnancies
Authors: Rosta Klara , Al-Bibawy Katharina , Al-Bibawy Maria , Temsch Wilhelm , Springer Stephanie , Somogyi Aniko , Ott Johannes
Published: July 2020

Background: In this study, we aimed to investigate the incidence of gestational diabetes mellitus (GDM) in women who carried twin pregnancies and received vaginal progesterone. Methods: In this retrospective cohort study, 203 out of 1686 women with twin pregnancies received natural progesterone (200 mg/day between gestational weeks 16 + 0 and 36 + 0) vaginally for ≥ 4 weeks. The control group consisted of 1483 women with twin pregnancies without progesterone administration. Pearson’s Chi squared test, Fisher’s exact test, and Student’s t-test was used to compare differences between the control and the progesterone-treated groups. A multivariate binary logistic regression was performed to assess relative independent associations on the dependent outcome of GDM incidence. Results: Vaginal progesterone treatment in twin pregnancies had no significant influence on developing GDM (p = 0.662). Higher pre-pregnancy BMI (OR 1.1; p < 0.001), GDM in previous pregnancy (OR 6.0; p < 0.001), and smoking during pregnancy (OR 1.6; p = 0.014) posed an increased risk for developing GDM. Conclusion: In twin pregnancies, the use of vaginal progesterone for the prevention of recurrent preterm delivery was not associated with an increased risk of GDM.
Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors
Authors: García-Gutiérrez Valentín , Hernández-Boluda Juan Carlos
Published: July 2020

Despite the excellent overall survival (OS) of patients with chronic myeloid leukemia (CML), a significant proportion will not achieve optimal response to imatinib or second-generation tyrosine kinase inhibitors (2GTKI). For patients with inadequate response to 2GTKIs, alternative 2GTKIs or ponatinib are widely available treatment options in daily clinical practice. Treatment decisions should be guided by correct identification of the cause of treatment failure and accurate distinction between resistant from intolerant or nonadherence patients. This review aims to provide practical advice on how to select the best treatment option in each clinical scenario.
Comprehensive Evaluation of the Oral Health Status, Salivary Gland Function, and Oxidative Stress in the Saliva of Patients with Subacute Phase of Stroke: A Case-Control Study
Authors: Gerreth Piotr , Maciejczyk Mateusz , Zalewska Anna , Gerreth Karolina , Hojan Katarzyna
Published: July 2020

This is the first study to assess, comprehensively, the oral health status; salivary glands’ function and enzymatic and non-enzymatic antioxidant defense; and oxidative damage to proteins and lipids in the non-stimulated (NWS) and stimulated (SWS) whole saliva of stroke patients. The study included 30 patients in the subacute phase of the stroke and an age and gender-matched control group. We showed that the activity of antioxidant enzymes (catalase and salivary peroxidase) was significantly higher in both NWS and SWS of stroke patients, similarly to uric acid concentration. However, in the study group, the reduced glutathione (GSH) concentration in SWS decreased. The contents of protein glycooxidation products (advanced glycation end products (AGE) and protein oxidation products (AOPP)) and lipid hydroperoxides were significantly higher in NWS and SWS of stroke patients. In the study group there was also a decrease in stimulated saliva secretion and total protein content. Interestingly, products of protein and lipid oxidation correlate negatively with SWS flow. The ROC analysis showed that salivary GSH with 100% specificity and 100% sensitivity differentiates the analyzed groups (AUC = 1.0). To sum up, in subacute stroke patients there are redox imbalances and oxidative damage to proteins and lipids in non-stimulated and stimulated saliva. Stroke patients also suffer from salivary gland dysfunction.
Influence of Care Pathway on Thyroid Nodule Surgery Relevance: A Historical Cohort Study
Authors: Castellnou Solène , Lifante Jean-Christophe , Polazzi Stéphanie , Pascal Léa , Borson-Chazot Françoise , Duclos Antoine
Published: July 2020

Background: Guidelines recommend using fine-needle aspiration cytology (FNAC) to guide thyroid nodule surgical indication. However, the extent to which these guidelines are followed remains unclear. This study aimed to analyze the quality of the preoperative care pathway and to evaluate whether compliance with the recommended care pathway influenced the relevance of surgical indications. Methods: Nationwide historical cohort study based on data from a sample (1/97th) of French health insurance beneficiaries. Evaluation of the care pathway of adult patients operated on between 2012 and 2015 during the year preceding thyroid nodule surgery. The pathway containing only FNAC was called “FNAC”, the pathway including an endocrinology consultation (ENDO) with FNAC was called “FNAC+ENDO”, whereas the no FNAC pathway was called “NO FNAC”. The main outcome was the malignant nature of the nodule. Results: Among the 1080 patients included in the study, “FNAC+ENDO” was found in 197 (18.2%), “FNAC” in 207 (19.2%), and “NO FNAC” in 676 (62.6%) patients. Cancer diagnosis was recorded in 72 (36.5%) “FNAC+ENDO” patients and 66 (31.9%) “FNAC” patients, against 119 (17.6%) “NO FNAC” patients. As compared to “NO FNAC”, the “FNAC+ENDO” care pathway was associated with thyroid cancer diagnosis (OR 2.67, 1.88–3.81), as was “FNAC” (OR 2.09, 1.46–2.98). Surgeries performed in university hospitals were also associated with thyroid cancer diagnosis (OR 1.61, 1.19–2.17). Increasing the year for surgery was associated with optimal care pathway (2015 vs. 2012, OR 1.52, 1.06–2.18). Conclusions: The recommended care pathway was associated with more relevant surgical indications. While clinical guidelines were insufficiently followed, compliance improved over the years.
Diagnostic Value of Six Thyroid Imaging Reporting and Data Systems (TIRADS) in Cytologically Equivocal Thyroid Nodules
Authors: Słowińska-Klencka Dorota , Wysocka-Konieczna Kamila , Klencki Mariusz , Popowicz Bożena
Published: July 2020

The aim was to compare the usefulness of selected thyroid sonographic risk-stratification systems in the diagnostics of nodules with indeterminate/suspicious cytology or unequivocal cytology in a population with a history of iodine deficiency. The diagnostic efficacy of ACR-TIRADS (the American College of Radiology Thyroid Imaging Reporting and Data Systems), EU-TIRADS (European Thyroid Association TIRADS), Korean-TIRADS, Kwak-TIRADS, AACE/ACE-AME-guidelines (American Association of Clinical Endocrinologists/ American College of Endocrinology-Associazione Medici Endocrinologi guidelines) and ATA-guidelines (American Thyroid Association guidelines) was evaluated in 1000 nodules with determined histopathological diagnosis: 329 FLUS/AUS (10.6% cancers), 167 SFN/SHT (11.6% cancers), 44 SM (77.3% cancers), 298 BL (benign lesions), 162 MN (malignant neoplasms). The percentage of PTC (papillary thyroid carcinoma) among cancers was higher in Bethesda MN (86.4%) and SM (suspicion of malignancy) nodules (91.2%) than in FLUS/AUS (57.1%, p < 0.005) and SFN/SHT (suspicion of follicular neoplasm/ suspicion of Hürthle cell tumor) nodules (36.8%, p < 0.001). TIRADS efficacy was higher for MN (AUC: 0.827–0.874) and SM nodules (AUC: 0.775–0.851) than for FLUS/AUS (AUC: 0.655–0.701) or SFN/SHT nodules (AUC: 0.593–0.621). FLUS/AUS (follicular lesion of undetermined significance/ atypia of undetermined significance) nodules assigned to a high risk TIRADS category had malignancy risk of 25%. In the SFN/SHT subgroup none TIRADS category changed nodule’s malignancy risk. EU-TIRADS and AACE/ACE-AME-guidelines would allow diagnosing the highest number of PTC, FTC (follicular thyroid carcinoma), HTC (Hürthle cell carcinoma), MTC (medullary thyroid carcinoma). The highest OR value was for Kwak-TIRADS (12.6) and Korean-TIRADS (12.0). Conclusions: TIRADS efficacy depends on the incidence of PTC among cancers. All evaluated TIRADS facilitate the selection of FLUS/AUS nodules for the surgical treatment but these systems are not efficient in the management of SFN/SHT nodules.
Identification of a Clinical Cutoff Value for Multiplex KRASG12/G13 Mutation Detection in Colorectal Adenocarcinoma Patients Using Digital Droplet PCR, and Comparison with Sanger Sequencing and PNA Clamping Assay
Authors: Lee Kyung Ha , Lee Tae Hee , Choi Min Kyung , Kwon In Sun , Bae Go Eun , Yeo Min-Kyung
Published: July 2020

KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) is a major predictive marker for anti-epidermal growth factor receptor treatment, and determination of KRAS mutational status is crucial for successful management of colorectal adenocarcinoma. More standardized and accurate methods for testing KRAS mutation, which is vital for therapeutic decision-making, are required. Digital droplet polymerase chain reaction (ddPCR) is an advanced digital PCR technology developed to provide absolute quantitation of target DNA. In this study, we validated the clinical performance of ddPCR in determination of KRAS mutational status, and compared ddPCR results with those obtained by Sanger sequencing and peptide nucleic acid-clamping. Of 81 colorectal adenocarcinoma tissue samples, three repeated sets of KRASG12/G13 mutation were measured by ddPCR, yielding high consistency (ICC = 0.956). Receiver operating characteristic (ROC) curves were constructed to determine KRASG12/G13 mutational status based on mutant allele frequency generated by ddPCR. Using the best threshold cutoff (mutant allele frequency of 7.9%), ddPCR had superior diagnostic sensitivity (100%) and specificity (100%) relative to the two other techniques. Thus, ddPCR is effective for detecting the KRASG12/G13 mutation in colorectal adenocarcinoma tissue samples. By allowing definition of the optimal cutoff, ddPCR represents a potentially useful diagnostic tool that could improve diagnostic sensitivity and specificity.
Chronic Rhinosinusitis—An Update on Epidemiology, Pathogenesis and Management
Authors: Albu Silviu
Published: July 2020

Chronic rhinosinusitis (CRS) is one of the most common chronic medical conditions worldwide, affecting all age groups [...]
Long-Term Follow-Up of Targeted Biopsy Yield (LOFTY Study) in Ulcerative Colitis Surveillance Colonoscopy
Authors: Hata Keisuke , Ishihara Soichiro , Ajioka Yoichi , Mitsuyama Keiichi , Watanabe Kenji , Hanai Hiroyuki , Kunisaki Reiko , Nakase Hiroshi , Matsuda Keiji , Iwakiri Ryuichi , Hida Nobuyuki , Tanaka Shinji , Takeuchi Yoshiaki , Shinozaki Masaru , Ogata Noriyuki , Moriichi Kentaro , Hirai Fumihito , Sugihara Kenichi , Hisamatsu Tadakazu , Suzuki Yasuo , Watanabe Mamoru , Hibi Toshifumi
Published: July 2020

We previously performed a randomized controlled trial (RCT) comparing targeted and random biopsy in neoplasia detection in patients with ulcerative colitis (UC), which showed the short-term effectiveness of targeted biopsy with one-time colonoscopy. In this retrospective cohort study, we investigated the long-term effectiveness of targeted biopsy in tertiary care hospitals, using the follow-up data from patients with UC for ≥ 8 years who had enrolled in the initial RCT. The primary outcome was death from colorectal cancer (CRC). Secondary outcomes were advanced neoplasia (CRC or high-grade dysplasia) and colectomy due to neoplasia after the RCT. We compared these outcomes between target and random groups. Data on 195 of the 221 patients (88.2%) enrolled in the previous RCT were collected from 28 institutions between 2008 and 2019. No patients died of CRC in either group, with a median 8.8-year follow-up demonstrating a robustness for targeted biopsy in terms of CRC death prevention. Advanced neoplasia was detected in four and three patients in the target and random groups, respectively. Colectomy was required due to neoplasia in three patients in each group. The chance of developing CRC in patients with a negative colonoscopy was low, and the targeted biopsy appeared effective in this population. Conversely, patients found with low-grade dysplasia at initial RCT have 10-fold higher risk of progression to high-grade dysplasia and/or CRC. Ten extracolonic malignancies were observed during the follow-up, resulting in four deaths. Panchromoendoscopy was used only in 4.6% and targeted biopsy was only performed in 59.1% of colonoscopies. We recommend targeted biopsy rather than > 33 random biopsies in real-world settings under adequate observation by specialists.