bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Modulation of 25-hydroxycholecalciferol on Innate Immunity of Broiler Breeder Hens
Authors: Chou Pao-Chia , Lin Pei-Chi , Wu Shu-Wei , Wang Chien-Kai , Chung Thau-Kiong , Walzem Rosemary L. , Lai Lih-Shiuh , Chen Shuen-Ei
Published: June 2021

Past immunological studies in broilers focused on juveniles within the rapid pre-slaughter growth period and may not reflect adult immune responses, particularly in breeders managed with chronic feed restriction (R). The study aimed to assess innate immune cell functions in respect to R vs. ad libitum (Ad) feed intake in breeder hens with and without dietary 25-hydroxycholecalciferol (25-OH-D3) supplementation. Ad-feed intake consistently suppressed IL-1β secretion, respiratory burst, and cell livability in peripheral heterophils and/or monocytes along the feeding trial from the age of 51 to 68 weeks. Supplemental 25-OH-D3 repressed IL-1β secretion and respiratory burst of both cells mostly in R-hens, but promoted monocyte phagocytosis, chemotaxis, and bacterial killing activity in Ad-hens in accompany with relieved hyperglycemia, hyperlipidemia, and systemic inflammation. Overnight cultures with leukocytes from R-hens confirmed the differential effects of 25-OH-D3 to rescue immune functions altered by glucose and/or palmitic acid exposure. Studies with specific inhibitors further manifested the operative mechanisms via glucolipotoxicity in a cell type- and function-dependent manner. The results concluded no predominant changes between R- vs. Ad-feed intake on leukocyte defense against pathogens despite some differential differences, but supplemental 25-OH-D3 exerts more pronounced effects in Ad-hens.
Molecular Characterization of KPC-2-Producing Enterobacter cloacae Complex Isolates from Cali, Colombia
Authors: Falco Aura , Guerrero Daniela , García Isabella , Correa Adriana , Rivera Sandra , Olaya María Beatriz , Aranaga Carlos
Published: June 2021

The Enterobacter cloacae complex is an emerging opportunistic pathogen whose increased resistance to carbapenems is considered a public health problem. This is due to the loss of efficacy of beta-lactam antibiotics, which are used as the first treatment option in the management of infections caused by Gram-negative bacteria. The objective of this study was to perform the molecular characterization of 28 isolates of the E. cloacae complex resistant to cephalosporins and carbapenems isolated between 2011 and 2018 from five hospitals located in the municipality of Santiago de Cali, Colombia. Molecular detection of blaKPC, blaVIM, blaNDM and blaOXA-48-like genes was performed on these isolates and the genetic relationship between the isolates was assessed using multilocus sequence typing (MLST). Forty-three percent of the isolates carried the blaKPC-2 gene variant. MLST showed high genetic diversity among isolates, the most frequent being the sequence type ST510 with a frequency of 50%. The identification of the genes involved in carbapenem resistance and dispersing genotypes is an important step toward the development of effective prevention and epidemiological surveillance strategies in Colombian hospitals.
Clinical and Instrumental TMJ Evaluation in Children and Adolescents with Juvenile Idiopathic Arthritis: A Case—Control Study
Authors: D’Attilio Michele , Di Carlo Beatrice , Caroccia Francesco , Moscagiuri Francesco , d’Angelo Debora Mariarita , Chiarelli Francesco , Festa Felice , Breda Luciana
Published: June 2021

To investigate temporomandibular joint (TMJ) involvement signs such as muscle pain, the ratio of masseter and temporal muscle activity, mouth opening width and jaw deviation during mouth opening in children and adolescents with juvenile idiopathic arthritis (JIA), a group of 32 subjects with JIA and a control group of 32 healthy subjects were evaluated. Data were collected clinically by muscle palpation (masseters, anterior temporalis and sternocleidomastoids) and instrumental analysis (electromyography and kinesiography). Higher pain was registered in the masseter and sternocleidomastoid muscles on both sides and in the right anterior temporalis in the JIA group compared to the control group (p < 0.05). Electromyography showed no statistically significant difference in the frequency of the pathological ratio of masseter and temporal muscle activity (MM/TA < 1) both in the JIA group and in the control group. Kinesiography showed a statistically significant difference in mouth opening width and jaw deviation during mouth opening between the groups (p < 0.05): JIA subjects showed lower mouth opening values and wider deviation on mouth opening; 29 out of 32 JIA subjects showed jaw deviation towards the right side. JIA affects the TMJ, causing myalgia in the head and neck muscles, a reduction in mouth opening width and an increase in jaw deviation during mouth opening.
A Parametric Product Design Framework for the Development of Mass Customized Head/Face (Eyewear) Products
Authors: Bai Xiaobo , Huerta Omar , Unver Ertu , Allen James , Clayton Jane E.
Published: June 2021

This study led to the development of a parametric design method for mass-customised head/face products. A systematic review of different approaches for mass customization was conducted, identifying advantages and limitations for their application to new product development. A parametric modelling algorithm of a 3D human face was developed using selected scanned 3D head models. The algorithm was developed from a set of measurable and adjustable parameter points related to the facial geometry. These parameters were defined using planimetry. Using the assigned parameter values as input, the parametric model generated 3D models of a human face that served as a reference for the design of customized eyewear. The current challenges and opportunities of mass customized head/face products are described, along with the possibilities for new parametric product design approaches to enable rapid manufacturing and mass customization. This study also explored whether a new parametric design framework for mass customization could be effectively implemented as an early-stage new product development strategy for head/face products.
Time-Domain Aeroelasticity Analysis by a Tightly Coupled Fluid-Structure Interaction Methodology
Authors: Liu Zhongyu , Nie Xueyuan , Zheng Guannan , Yang Guowei
Published: June 2021

A tightly coupled fluid-structure interaction (FSI) methodology is developed for aeroelasticity analysis in the time domain. The preconditioned Navier–Stokes equations for all Mach numbers are employed and the structural equations are tightly coupled with the fluid equations by discretizing their time derivative term in the same pseudo time-stepping method. A modified mesh deformation method based on reduced control points radial basis functions (RBF) is utilized, and a RBF based mapping algorithm is introduced for data exchange on the interaction interface. To evaluate the methodology, the flutter boundary and the limit cycle oscillation of Isogai wing and the flutter boundary of AGARD 445.6 wing are analyzed and validated.
Method for Robot Manipulator Joint Wear Reduction by Finding the Optimal Robot Placement in a Robotic Cell
Authors: Kot Tomáš , Bobovský Zdenko , Vysocký Aleš , Krys Václav , Šafařík Jakub , Ružarovský Roman
Published: June 2021

We describe a method for robotic cell optimization by changing the placement of the robot manipulator within the cell in applications with a fixed end-point trajectory. The goal is to reduce the overall robot joint wear and to prevent uneven joint wear when one or several joints are stressed more than the other joints. Joint wear is approximated by calculating the integral of the mechanical work of each joint during the whole trajectory, which depends on the joint angular velocity and torque. The method relies on using a dynamic simulation for the evaluation of the torques and velocities in robot joints for individual robot positions. Verification of the method was performed using CoppeliaSim and a laboratory robotic cell with the collaborative robot UR3. The results confirmed that, with proper robot base placement, the overall wear of the joints of a robotic arm could be reduced from 22% to 53% depending on the trajectory.
Surface Forming Criteria of Ti-6AL-4V Titanium Alloy under Laser Loading
Authors: Yin Fei , Ye Xia , Yao Hongbing , Wei Pengyu , Wang Xumei , Cong Jiawei , Tong Yanqun
Published: June 2021

In order to study the spallation phenomenon of titanium alloy under the shock of nanosecond laser, the Neodymium-Yttrium-Aluminum Garnet laser was used to carry out laser shock experiments on the surface of titanium alloy. By observing and measuring the surface morphology of the target material, the forming factors and the changes of the surface morphology under different parameter settings, the forming criteria of the titanium alloy were obtained. The results show that under the single variable method, the change of laser energy can affect the target shape variable, and there is a positive correlation between them. When the thickness was greater than or equal to 0.08 mm, no obvious cracks were found in the targets. Moreover, the number of impact times was the key factor for the target deformation; with the growth of impact times, the target deformation gradually became larger until the crack appeared. The larger the diameter of the spot, the more likely the target was to undergo plastic deformation. The surface of titanium alloy with a thickness of 0.08 mm appeared to rebound under specific laser shock condition. The changes in the back of the target material were observed in real time through a high-speed camera, and the plasma induced by the laser was observed in the process. This study is based on the results of previous studies to obtain the titanium alloy forming criteria, which provides a basis for the setting of laser parameters and the thickness of the target when the nanosecond laser impacts the Ti-6AL-4V target.
Regularized Chained Deep Neural Network Classifier for Multiple Annotators
Authors: Gil-González Julián , Valencia-Duque Andrés , Álvarez-Meza Andrés , Orozco-Gutiérrez Álvaro , García-Moreno Andrea
Published: June 2021

The increasing popularity of crowdsourcing platforms, i.e., Amazon Mechanical Turk, changes how datasets for supervised learning are built. In these cases, instead of having datasets labeled by one source (which is supposed to be an expert who provided the absolute gold standard), databases holding multiple annotators are provided. However, most state-of-the-art methods devoted to learning from multiple experts assume that the labeler’s behavior is homogeneous across the input feature space. Besides, independence constraints are imposed on annotators’ outputs. This paper presents a regularized chained deep neural network to deal with classification tasks from multiple annotators. The introduced method, termed RCDNN, jointly predicts the ground truth label and the annotators’ performance from input space samples. In turn, RCDNN codes interdependencies among the experts by analyzing the layers’ weights and includes l1, l2, and Monte-Carlo Dropout-based regularizers to deal with the over-fitting issue in deep learning models. Obtained results (using both simulated and real-world annotators) demonstrate that RCDNN can deal with multi-labelers scenarios for classification tasks, defeating state-of-the-art techniques.
Evaluation of 3-Methylbutanoic Acid Methyl Ester as a Factor Influencing Flavor Cleanness in Arabica Specialty Coffee
Authors: Iwasa Keiko , Seta Harumichi , Matsuo Yoshihide , Nakahara Koichi
Published: June 2021

This paper reports on the chemical compounds in arabica coffee beans with a high Specialty Coffee Association (SCA) cupping score, especially those in specialty coffee beans. We investigated the relationship between the chemical compounds and cupping scores by considering 16 types of Coffea arabica (arabica coffee) beans from Guatemala (SCA cupping score of 76.5–89.0 points). Non-targeted gas chromatography-mass spectrometry-based chemometric profiling indicated that specialty beans with a high cupping score contained considerable amounts of methyl-esterified compounds (MECs), including 3-methylbutanoic acid methyl ester (3-MBM), and other fatty acid methyl esters. The effect of MECs on flavor quality was verified by spiking the coffee brew with 3-MBM, which was the top-ranked component, as obtained through a regression model associated with cupping scores. Notably, 3-MBM was responsible for the fresh-fruity aroma and cleanness of the coffee brew. Although cleanness is a significant factor for specialty beans, the identification of compounds that contribute to cleanness has not been reported in previous research. The chemometric profiling approach coupled with spiking test validation will improve the identification and characterization of 3-MBM commonly found in arabica specialty beans. Therefore, 3-MBM, either alone or together with MECs, can be used as a marker in coffee production.
Simulation and Experimental Study of the Near Field Probe in the Form of a Folded Dipole for Measuring Glucose Concentration
Authors: Gorst Aleksandr , Zavyalova Kseniya , Mironchev Aleksandr , Zapasnoy Andrey , Klokov Andrey
Published: June 2021

The article investigates the near-field probe of a special design to account for changes in glucose concentration. The probe is designed in such a way that it emits radiation in both directions from its plane. In this paper, it was proposed to modernize this design and consider the unidirectional emission of the probe in order to maximize the signal and reduce energy loss. We have done extensive research for both bidirectional and unidirectional probe designs. Numerical simulations and field experiments were carried out to determine different concentrations of glucose (0, 4, 5.3, 7.5 mmol/L). Numerical modeling of a unidirectional probe showed that the interaction of radiation generated by such a probe with a multilayer structure simulating a human hand showed a better result and high sensitivity compared to a bidirectional probe. Further, based on the simulation results, a phantom (physical model) of a human hand was recreated from layers with dielectric properties as close as possible to the properties of materials during simulation. The probe was constructed from a copper tube and matched both the geometric and physical parameters of the model. The experimental measurement was carried out using a vector network analyzer in the frequency range 2–10 GHz. The experimental measurement was carried out using a vector network analyzer in the frequency range 2–10 GHz for the unidirectional and bidirectional probes. Further, the results of the experiment were compared with the results of numerical simulation. According to the results of multiple experiments, it was found that the average deviation between the concentrations was 2 dB for a unidirectional probe and 0.4 dB for a bidirectional probe. Thus, the sensitivity of the unidirectional probe was 1.5 dB/(mmol/L) for the bidirectional one 0.3 dB/(mmol/L). Thus, the improved design of the near-field probe can be used to record glucose concentrations.
A Collaborative Filtering Algorithm with Intragroup Divergence for POI Group Recommendation
Authors: Liu Yanheng , Yin Minghao , Zhou Xu
Published: June 2021

The purpose of POI group recommendation is to generate a recommendation list of locations for a group of users. Most of the current studies first conduct personal recommendation and then use recommendation strategies to integrate individual recommendation results. Few studies consider the divergence of groups. To improve the precision of recommendations, we propose a POI group recommendation method based on collaborative filtering with intragroup divergence in this paper. Firstly, user preference vector is constructed based on the preference of the user on time and category. Furthermore, a computation method similar to TF-IDF is presented to compute the degree of preference of the user to the category. Secondly, we establish a group feature preference model, and the similarity of the group and other users’ feature preference is obtained based on the check-ins. Thirdly, the intragroup divergence of POIs is measured according to the POI preference of group members and their friends. Finally, the preference rating of the group for each location is calculated based on a collaborative filtering method and intragroup divergence computation, and the top-ranked score of locations are the recommendation results for the group. Experiments have been conducted on two LBSN datasets, and the experimental results on precision and recall show that the performance of the proposed method is superior to other methods.
Is Small Scale Desalination Coupled with Renewable Energy a Cost-Effective Solution?
Authors: Kyriakarakos George , Papadakis George
Published: June 2021

Water and energy are two of the most important inputs for a community to thrive. While water is dominant on earth, only 2.5% of the water is fresh water and over 98% of that water is either ground water or locked up in glaciers and ice caps. Therefore, only about 1.2% of all the freshwater is surface water which is able to meet human needs. About 2 billion people currently do not have sufficient access to fresh water. One of the solutions deployed in the last decades for island and coastal areas has been desalination. Desalination of seawater and brackish groundwater is commercially available and still a fast-advancing technology. The decreasing cost of renewable energy coupled with strategies based on renewables for powering populations without access to electricity and policies for complete decarbonization of the economy such as the European Green Deal make the combination of renewables and desalination a really interesting approach. This paper investigates combinations of small-scale RO desalination systems which are able to produce up to a few thousand m3 of desalinated water per day coupled with photovoltaic (PV) and wind energy systems, both in grid-connected, as well as in autonomous scenarios. The results show that RO desalination coupled with renewables can address cost-effectively the current issues in terms of water scarcity, while minimizing the environmental footprint of the process. In this paper, it has been showcased that desalination powered by renewables can be deployed in practically any location on earth having access to sea or a brackish water source. The results show that even for grid-connected systems it is more cost-effective and profitable to include a renewable energy system to power the plant, apart from the corresponding environmental benefits.
Effectiveness of Tree Pattern in Street Canyons on Thermal Conditions and Human Comfort. Assessment of an Urban Renewal Project in Historical District in Lodz (Poland)
Authors: Bochenek Anna Dominika , Klemm Katarzyna
Published: June 2021

The implementation of adaptation strategies has become an essential activity of spatial planning departments. Passive technologies related to the introduction of natural components in the form of vegetation are used, especially in urban development plans, to mitigate the effects of climate change and thus improve the quality of citizen life. Nature-Based Solutions are of particular importance in the areas of strict city centers, where historical building structures are subject to legal protection. In this study, the authors tested the influence of high greenery on the microclimatic conditions in the areas of typical street canyons (east–west and north–south orientations). Authors included the established greenery strategy by the City Planning Department. To estimate the impact of the assumed scenarios, a CFD tool was used—the ENVI-met application, which is commonly used in the field of urban microclimatology. Studies have shown that the introduction of 10% of green area contributed to a maximum air temperature reduction of 0.80 °C (17:00) in an east–west-oriented canyon, 0.49 °C (10:00) in a north–south canyon. The scenarios, assumed by the City Planning Department, related to the introduction of a greater amount of greenery turned out to be a less effective solution. The impact of greenery on the thermal comfort felt by humans was also determined. The reduction in the PET index was a maximum of 10.80 °C (14:00) in an east–west canyon; 6.66 °C (14:00) in a canyon area with a north–south orientation. This research might constitute the foundations to a re-evaluation of the urban development plans. The outcomes can lead to taking alternative direction of city layout transformations.
Coarse Technogenic Material in Urban Surface Deposited Sediments (USDS)
Authors: Seleznev Andrian , Ilgasheva Ekaterina , Yarmoshenko Ilia , Malinovsky Georgy
Published: June 2021

In the current paper, the analysis of heavy mineral concentrate (Schlich analysis) was used to study the particles of technogenic origin in the samples of urban surface-deposited sediments (USDS). The USDS samples were collected in the residential areas of 10 Russian cities located in different economic, climatic, and geological zones: Ufa, Perm, Tyumen, Chelyabinsk, Nizhny Tagil, Magnitogorsk, Nizhny Novgorod, Rostov-on-Don, Murmansk, and Ekaterinburg. The number of technogenic particles was determined in the coarse particle size fractions of 0.1–0.25 and 0.25–1 mm. The types of technogenic particle were studied by scanning electron microscopy (SEM) analysis. The amount of technogenic material differed from city to city; the fraction of technogenic particles in the samples varied in the range from 0.01 to 0.43 with an average value of 0.18. The technogenic particles in USDS samples were represented by lithoid and granulated slag, iron and silicate microspheres, fragments of brick, paint, glass, plaster, and other household waste. Various types of technogenic particle differed in morphological characteristics as well as in chemical composition. The novelty and significance of the study comprises the following: it has been shown that technogenic particles are contained in a significant part of the USDS; the quantitative indicators of the accumulation of technogenic particles in the urban landscape have been determined; the contributions of various types of particles to the total amount of technogenic material were estimated for the urban landscape; the trends in the transformation of typomorphic elemental associations in the urban sediments associated with the material of technogenic origin were demonstrated; and the alteration trends in the USDS microelemental content were revealed, taking into account the impurities in the composition of technogenic particles.
adipoSIGHT in Therapeutic Response: Consequences in Osteosarcoma Treatment
Authors: Kundu Banani , Brancato Virginia , Oliveira Joaquim , Correlo Vitor M. , Reis Rui L. , Kundu Subhas C.
Published: June 2021

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo (osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell–cell interaction is investigated by means of E-cadherin expression. Comparatively high expression of E-cadherin and compact organization is observed in heterotypic tumorspheres (Saos 2–ASCs) compared to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic. In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and warrants further investigation.
Physiological and Psychological Effects of Treadmill Overtraining Implementation
Authors: Chung Yi , Hsiao Yi-Ting , Huang Wen-Ching
Published: June 2021

Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.
A Reliable and Standardizable Differential PCR and qPCR Methodology Assesses HER2 Gene Amplification in Gastric Cancer
Authors: Juarez Ignacio , Toro-Fernandez Juan Francisco , Vaquero-Yuste Christian , Molina-Alejandre Marta , Lasa Inmaculada , Gomez Remedios , Lopez Adela , Martin-Villa Jose Manuel , Gutierrez Alberto
Published: June 2021

We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.
Breast Cancer Detection from a Urine Sample by Dog Sniffing: A Preliminary Study for the Development of a New Screening Device, and a Literature Review
Authors: Kure Shoko , Iida Shinya , Yamada Marina , Takei Hiroyuki , Yamashita Naoyuki , Sato Yuji , Miyashita Masao
Published: June 2021

Background: Breast cancer is a leading cause of cancer death worldwide. Several studies have demonstrated that dogs can sniff and detect cancer in the breath or urine sample of a patient. This study aims to assess whether the urine sample can be used for breast cancer screening by its fingerprints of volatile organic compounds using a single trained sniffer dog. This is a preliminary study for developing the “electronic nose” for cancer screening. Methods: A nine-year-old female Labrador Retriever was trained to identify cancer from urine samples of breast cancer patients. Urine samples from patients histologically diagnosed with primary breast cancer, those with non-breast malignant diseases, and healthy volunteers were obtained, and a double-blind test was performed. Total of 40 patients with breast cancer, 142 patients with non-breast malignant diseases, and 18 healthy volunteers were enrolled, and their urine samples were collected. Results: In 40 times out of 40 runs of a double-blind test, the trained dog could correctly identify urine samples of breast cancer patients. Sensitivity and specificity of this breast cancer detection method using dog sniffing were both 100%. Conclusions: The trained dog in this study could accurately detect breast cancer from urine samples of breast cancer patients. These results indicate the feasibility of a method to detect breast cancer from urine samples using dog sniffing in the diagnosis of breast cancer. Although the methodological standardization is still an issue to be discussed, the current result warrants further study for developing a new breast cancer screening method based on volatile organic compounds in urine samples.
Bicarbonate Evokes Reciprocal Changes in Intracellular Cyclic di-GMP and Cyclic AMP Levels in Pseudomonas aeruginosa
Authors: Ruksakiet Kasidid , Stercz Balázs , Tóth Gergő , Jaikumpun Pongsiri , Gróf Ilona , Tengölics Roland , Lohinai Zsolt M. , Horváth Péter , Deli Mária A. , Steward Martin C. , Dobay Orsolya , Zsembery Ákos
Published: June 2021

The formation of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) is one of the most common causes of morbidity and mortality in CF patients. Cyclic di-GMP and cyclic AMP are second messengers regulating the bacterial lifestyle transition in response to environmental signals. We aimed to investigate the effects of extracellular pH and bicarbonate on intracellular c-di-GMP and cAMP levels, and on biofilm formation. P. aeruginosa was inoculated in a brain–heart infusion medium supplemented with 25 and 50 mM NaCl in ambient air (pH adjusted to 7.4 and 7.7 respectively), or with 25 and 50 mM NaHCO3 in 5% CO2 (pH 7.4 and 7.7). After 16 h incubation, c-di-GMP and cAMP were extracted and their concentrations determined. Biofilm formation was investigated using an xCelligence real-time cell analyzer and by crystal violet assay. Our results show that HCO3− exposure decreased c-di-GMP and increased cAMP levels in a dose-dependent manner. Biofilm formation was also reduced after 48 h exposure to HCO3−. The reciprocal changes in second messenger concentrations were not influenced by changes in medium pH or osmolality. These findings indicate that HCO3− per se modulates the levels of c-di-GMP and cAMP, thereby inhibiting biofilm formation and promoting the planktonic lifestyle of the bacteria.
The Role of the Bisphenol A in Diabetes and Obesity
Authors: Pérez-Bermejo Marcelino , Mas-Pérez Irene , Murillo-Llorente Maria Teresa
Published: June 2021

Bisphenol A is a compound commonly found in products meant for daily use. It was one of the first compounds to be identified as an endocrine disruptor that was capable of disrupting the endocrine system and producing very similar effects to those of metabolic syndrome. It has recently gained popularity in the scientific arena as a risk factor for obesity and diabetes due to its ability to imitate natural oestrogens and bind to their receptors. The aim was to study the possible relationship between the Bisphenol A endocrine disruptor with diabetes and obesity. The analysis of the articles allows us to conclude that Bisphenol A is an additional risk factor to consider in the development of diabetes and obesity, since it is capable of stimulating the hypertrophy of adipocytes and altering the endocrine system by mimicking the effects of the oestrogen molecule, since epidemiological studies carried out have suggested that the same disruptions seen in experimental studies on animals can be found in humans; however, despite many countries having developed policies to limit exposure to this disruptor in their populations, there is a lack of international agreement. Understanding its relationship with obesity and diabetes will help to raise awareness in the population and adopt public health campaigns to prevent exposure—especially among young people—to these substances.
Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary Success
Authors: Racchetti Gabriella , Meldolesi Jacopo
Published: June 2021

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.
Biomarkers in Early Response to Brolucizumab on Pigment Epithelium Detachment Associated with Exudative Age-Related Macular Degeneration
Authors: Rispoli Marco , Eandi Chiara M. , Di Antonio Luca , Kilian Raphael , Montesel Andrea , Savastano Maria C.
Published: June 2021

Background: The purpose of this study was to describe early changes in the morphology of pigment epithelium detachments (PED) after an intravitreal injection of Brolucizumab into eyes with macular neovascularization secondary to exudative age-related macular degeneration (e-AMD). Method: We included twelve eyes of 12 patients with PED secondary to e-AMD which were not responding to prior anti-VEGF treatments. An ophthalmic examination and an assessment of PED-horizontal maximal diameter (PED-HMD), PED-maximum high (PED-MH) and macular neovascularization (MNV) flow area (MNV-FA) by the means of structural optical coherence tomography (OCT) and OCT Angiography (OCT-A) were performed at baseline, as well as 1, 7, 14 and 30 days after the injection. Results: The mean age of the population of study was 78.4 (SD ± 4.8). The mean number of previous Ranibizumab or Aflibercept injections was 13 (SD ± 8). At the last follow-up visit, the PED-HMD did not significantly change (p = 0.16; F(DF:1.94, 20,85) = 1.9), the PED-MH showed a significant reduction [p = 0.01; F(DF:1.31, 14.13) = 6.84.] and the MNV-FA did not significantly differ (p = 0.1; F(1.97, 21.67) = 2.54) from baseline. No signs of ocular inflammation were observed during follow-up. Conclusions: A single Brolucizumab injection was able to determine the short-term effects on PEDs’ anatomical features of eyes with an unresponsive e-AMD.
A Meta-Integrative Qualitative Study on the Hidden Threats of Smart Buildings/Cities and Their Associated Impacts on Humans and the Environment
Authors: Raveendran Reshna , Tabet Aoul Kheira
Published: June 2021

Smart buildings deploying 5G and the Internet of Things (IoT) are viewed as the next sustainable solution that can be seamlessly integrated in all sectors of the built environment. The benefits are well advertised and range from inducing wellness and monitoring health, amplifying productivity, to energy savings. Comparatively, potential negative risks are less known and mostly relate to cyber-security threats and radiation effects. This meta-integrative qualitative synthesis research sought to determine the possible underlying demerits from developing smart buildings, and whether they outweigh the possible benefits. The study identified five master themes as threats of smart buildings: a surfeit of data centers, the proliferation of undersea cables, the consternation of cyber-security threats, electromagnetic pollution, and E-waste accumulation. Further, the paper discusses the rebound impacts on humans and the environment as smart buildings’ actualization becomes a reality. The study reveals that, although some aspects of smart buildings do have their tangible benefits, the potential repercussions from these not-so-discussed threats could undermine the former when all perspectives and interactions are analyzed collectively rather than in isolation.
Metabolic Rewiring and the Characterization of Oncometabolites
Authors: Beyoğlu Diren , Idle Jeffrey R.
Published: June 2021

The study of low-molecular-weight metabolites that exist in cells and organisms is known as metabolomics and is often conducted using mass spectrometry laboratory platforms. Definition of oncometabolites in the context of the metabolic phenotype of cancer cells has been accomplished through metabolomics. Oncometabolites result from mutations in cancer cell genes or from hypoxia-driven enzyme promiscuity. As a result, normal metabolites accumulate in cancer cells to unusually high concentrations or, alternatively, unusual metabolites are produced. The typical oncometabolites fumarate, succinate, (2R)-hydroxyglutarate and (2S)-hydroxyglutarate inhibit 2-oxoglutarate-dependent dioxygenases, such as histone demethylases and HIF prolyl-4-hydroxylases, together with DNA cytosine demethylases. As a result of the cancer cell acquiring this new metabolic phenotype, major changes in gene transcription occur and the modification of the epigenetic landscape of the cell promotes proliferation and progression of cancers. Stabilization of HIF1α through inhibition of HIF prolyl-4-hydroxylases by oncometabolites such as fumarate and succinate leads to a pseudohypoxic state that promotes inflammation, angiogenesis and metastasis. Metabolomics has additionally been employed to define the metabolic phenotype of cancer cells and patient biofluids in the search for cancer biomarkers. These efforts have led to the uncovering of the putative oncometabolites sarcosine, glycine, lactate, kynurenine, methylglyoxal, hypotaurine and (2R,3S)-dihydroxybutanoate, for which further research is required.
Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO)
Authors: Kirschner Martin , do Ó Hartmann Nicole , Parmentier Stefani , Hart Christina , Henze Larissa , Bisping Guido , Griesshammer Martin , Langer Florian , Pabinger-Fasching Ingrid , Matzdorff Axel , Riess Hanno , Koschmieder Steffen
Published: June 2021

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.
Relationship between Lung Carcinogenesis and Chronic Inflammation in Rodents
Authors: Nakano-Narusawa Yuko , Yokohira Masanao , Yamakawa Keiko , Ye Juanjuan , Tanimoto Misa , Wu Linxuan , Mukai Yuri , Imaida Katsumi , Matsuda Yoko
Published: June 2021

Lung cancer remains the leading cause of cancer-related deaths, with an estimated 1.76 million deaths reported in 2018. Numerous studies have focused on the prevention and treatment of lung cancer using rodent models. Various chemicals, including tobacco-derived agents induce lung cancer and pre-cancerous lesions in rodents. In recent years, transgenic engineered rodents, in particular, those generated with a focus on the well-known gene mutations in human lung cancer (KRAS, EGFR, and p53 mutations) have been widely studied. Animal studies have revealed that chronic inflammation significantly enhances lung carcinogenesis, and inhibition of inflammation suppresses cancer progression. Moreover, the reduction in tumor size by suppression of inflammation in animal experiments suggests that chronic inflammation influences the promotion of tumorigenesis. Here, we review rodent lung tumor models induced by various chemical carcinogens, including tobacco-related carcinogens, and transgenics, and discuss the roles of chronic inflammation in lung carcinogenesis.
Feasibility, Safety and Impact on Overall Survival of Awake Resection for Newly Diagnosed Supratentorial IDH-Wildtype Glioblastomas in Adults
Authors: Moiraghi Alessandro , Roux Alexandre , Peeters Sophie , Pelletier Jean-Baptiste , Baroud Marwan , Trancart Bénédicte , Oppenheim Catherine , Lechapt Emmanuèle , Benevello Chiara , Parraga Eduardo , Varlet Pascale , Chrétien Fabrice , Dezamis Edouard , Zanello Marc , Pallud Johan
Published: June 2021

Background: Although awake resection using intraoperative cortico-subcortical functional brain mapping is the benchmark technique for diffuse gliomas within eloquent brain areas, it is still rarely proposed for IDH-wildtype glioblastomas. We have assessed the feasibility, safety, and efficacy of awake resection for IDH-wildtype glioblastomas. Methods: Observational single-institution cohort (2012–2018) of 453 adult patients harboring supratentorial IDH-wildtype glioblastomas who benefited from awake resection, from asleep resection, or from a biopsy. Case matching (1:1) criteria between the awake group and asleep group: gender, age, RTOG-RPA class, tumor side, location and volume and neurosurgeon experience. Results: In patients in the awake resection subgroup (n = 42), supratotal resections were more frequent (21.4% vs. 3.1%, p < 0.0001) while partial resections were less frequent (21.4% vs. 40.1%, p < 0.0001) compared to the asleep (n = 222) resection subgroup. In multivariable analyses, postoperative standard radiochemistry (aHR = 0.04, p < 0.0001), supratotal resection (aHR = 0.27, p = 0.0021), total resection (aHR = 0.43, p < 0.0001), KPS score > 70 (HR = 0.66, p = 0.0013), MGMT promoter methylation (HR = 0.55, p = 0.0031), and awake surgery (HR = 0.54, p = 0.0156) were independent predictors of overall survival. After case matching, a longer overall survival was found for awake resection (HR = 0.47, p = 0.0103). Conclusions: Awake resection is safe, allows larger resections than asleep surgery, and positively impacts overall survival of IDH-wildtype glioblastoma in selected adult patients.
The Impact of an Ultra-Early Postoperative MRI on Treatment of Lower Grade Glioma
Authors: Pala Andrej , Durner Gregor , Braun Michael , Schmitz Bernd , Wirtz Christian Rainer , Coburger Jan
Published: June 2021

The timing of MRI imaging after surgical resection may have an important role in assessing the extent of resection (EoR) and in determining further treatment. The aim of our study was to evaluate the time dependency of T2 and FLAIR changes after surgery for LGG. The Log-Glio database of patients treated at our hospital from 2016 to 2021 was searched for patients >18a and non-enhancing intra-axial lesion with complete MR-imaging protocol. A total of 16 patients matched the inclusion criteria and were thus selected for volumetric analysis. All patients received an intraoperative scan (iMRI) after complete tumor removal, an ultra-early postoperative scan after skin closure, an early MRI within 48 h and a late follow up MRI after 3–4 mo. Detailed volumetric analysis of FLAIR and T2 abnormalities was conducted. Demographic data and basic characteristics were also analyzed. An ultra-early postoperative MRI was performed within a median time of 30 min after skin closure and showed significantly lower FLAIR (p = 0.003) and T2 (p = 0.003) abnormalities when compared to early postoperative MRI (median 23.5 h), though no significant difference was found between ultra-early and late postoperative FLAIR (p = 0.422) and T2 (p = 0.575) images. A significant difference was calculated between early and late postoperative FLAIR (p = 0.005) and T2 (p = 0.019) MRI scans. Additionally, we found no significant difference between intraoperative and ultra-early FLAIR/T2 (p = 0.919 and 0.499), but we found a significant difference between iMRI and early MRI FLAIR/T2 (p = 0.027 and p = 0.035). Therefore, a postoperative MRI performed 24 h or 48 h might lead to false positive findings. An MRI scan in the first hour after surgery (ultra-early) correlated best with residual tumor at 3 months follow up. An iMRI with open skull, at the end of resection, was similar to an ultra-early MRI with regard to residual tumor.