bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Phenolic, Anthocyanins HPLC-DAD-MS Determination and Antioxidant Capacity in Black Grape Skins and Blackberries: A Comparative Study
Authors: Paun Nadia , Botoran Oana Romina , Niculescu Violeta-Carolina
Published: January 2022

Anthocyanins are flavonoids with an antioxidant effect. They are the pigments that give rich colours to berries, red onions, pomegranates, and grapes. In addition to acting as antioxidants and fighting free radicals, anthocyanins may offer anti-inflammatory, anti-viral, and anti-cancer benefits. Among various types of fruits, blackberries and grapes are distinguished by their rich content in polyphenols, including anthocyanins. The purpose of this study was the identification and quantification of the anthocyanins in black grape skins and blackberries, but also the determination of the total phenolic content and total antioxidant capacity. The grape skins and blackberry extracts were prepared by an ultrasound-assisted acidified ethanol and methanol extraction method, with the 80% methanol solution being the most effective. Alcoholic extracts of blackberries and grape skins were analysed by the HPLC-DAD-MS method. There were five glycosylated anthocyanin compounds in blackberries, eight glycosylated anthocyanins compounds, and seven fragments of anthocyanin derivatives in grape skins identified. It was concluded that the anthocyanin profile of blackberries and grapes revealed mainly anthocyanin monoglycosides and acetylglycosides. Cyanidin-3-glucoside was the main component (86.49%) in blackberries, while, in the grape skins, the main component was delphinidin-3-O-glucoside (about 40.64%). Principal component analysis (PCA) was carried out on the basis of the 13 identified compounds in order to separate the extracts and describe the anthocyanins characteristics of different groups, the findings being in agreement with the experimental results. Compared to methanol extracts, ethanol extracts showed higher antioxidant activity, being related to the total phenolic content for the blackberries. Overall, the obtained results indicated that the blackberries and grapes skins possessed a high antioxidant content, similar to other berries, highlighting their potential use as fresh functional foods or fruit-derived products.
Smart Industrial Robot Control Trends, Challenges and Opportunities within Manufacturing
Authors: Arents Janis , Greitans Modris
Published: January 2022

Industrial robots and associated control methods are continuously developing. With the recent progress in the field of artificial intelligence, new perspectives in industrial robot control strategies have emerged, and prospects towards cognitive robots have arisen. AI-based robotic systems are strongly becoming one of the main areas of focus, as flexibility and deep understanding of complex manufacturing processes are becoming the key advantage to raise competitiveness. This review first expresses the significance of smart industrial robot control in manufacturing towards future factories by listing the needs, requirements and introducing the envisioned concept of smart industrial robots. Secondly, the current trends that are based on different learning strategies and methods are explored. Current computer-vision, deep reinforcement learning and imitation learning based robot control approaches and possible applications in manufacturing are investigated. Gaps, challenges, limitations and open issues are identified along the way.
High-Precision SLAM Based on the Tight Coupling of Dual Lidar Inertial Odometry for Multi-Scene Applications
Authors: Xiao Kui , Yu Wentao , Liu Weirong , Qu Feng , Ma Zhenyan
Published: January 2022

Simultaneous Localization and Mapping (SLAM) is an essential feature in many applications of mobile vehicles. To solve the problem of poor positioning accuracy, single use of mapping scene, and unclear structural characteristics in indoor and outdoor SLAM, a new framework of tight coupling of dual lidar inertial odometry is proposed in this paper. Firstly, through external calibration and an adaptive timestamp synchronization algorithm, the horizontal and vertical lidar data are fused, which compensates for the narrow vertical field of view (FOV) of the lidar and makes the characteristics of vertical direction more complete in the mapping process. Secondly, the dual lidar data is tightly coupled with an Inertial Measurement Unit (IMU) to eliminate the motion distortion of the dual lidar odometry. Then, the value of the lidar odometry after correcting distortion and the pre-integrated value of IMU are used as constraints to establish a non-linear least-squares objective function. Joint optimization is then performed to obtain the best value of the IMU state values, which will be used to predict the state of IMU at the next time step. Finally, experimental results are presented to verify the effectiveness of the proposed method.
Prospective Pilot Study of Immediately Provisionalized Restorations of Trabecular Metal-Enhanced Titanium Dental Implants: A 5-Year Follow-Up Report
Authors: van der Schoor Peter , Schlee Markus , Wen Hai-Bo
Published: January 2022

Porous tantalum trabecular metal biomaterial has a similar structure to trabecular bone, and was recently added to titanium dental implants as a surface enhancement. The purpose of this prospective pilot study was to describe 5-year survival results and crestal bone level changes around immediately-provisionalized Trabecular Metal Dental Implants. Eligible patients were adults in need of ≥1 implants in the posterior jaw. A non-occluding single acrylic provisional crown was in place for up to 14 days before final restoration. Clinical evaluations with radiographs were conducted at each follow-up visit (1 month, 3 months, 6 months, and 1 to 5 years). The primary endpoint was implant survival, characterized using the Kaplan-Meier method. The secondary endpoint was changes in crestal bone level, evaluated using a paired t-test to compare mean crestal bone levels between the baseline, 6-month, and annual follow-up values. In total, 30 patients (37 implants) were treated. Mean patient age was 45.5 years, and 63% were female. There was one implant failure; cumulative survival at 5 years was 97.2%. After the initial bone loss of 0.40 mm in the first 6 months, there were no statistically significant changes in crestal bone level over time up to 5 years of follow-up.
Hybrid Deep Reinforcement Learning for Pairs Trading
Authors: Kim Sang-Ho , Park Deog-Yeong , Lee Ki-Hoon
Published: January 2022

Pairs trading is an investment strategy that exploits the short-term price difference (spread) between two co-moving stocks. Recently, pairs trading methods based on deep reinforcement learning have yielded promising results. These methods can be classified into two approaches: (1) indirectly determining trading actions based on trading and stop-loss boundaries and (2) directly determining trading actions based on the spread. In the former approach, the trading boundary is completely dependent on the stop-loss boundary, which is certainly not optimal. In the latter approach, there is a risk of significant loss because of the absence of a stop-loss boundary. To overcome the disadvantages of the two approaches, we propose a hybrid deep reinforcement learning method for pairs trading called HDRL-Trader, which employs two independent reinforcement learning networks; one for determining trading actions and the other for determining stop-loss boundaries. Furthermore, HDRL-Trader incorporates novel techniques, such as dimensionality reduction, clustering, regression, behavior cloning, prioritized experience replay, and dynamic delay, into its architecture. The performance of HDRL-Trader is compared with the state-of-the-art reinforcement learning methods for pairs trading (P-DDQN, PTDQN, and P-Trader). The experimental results for twenty stock pairs in the Standard & Poor’s 500 index show that HDRL-Trader achieves an average return rate of 82.4%, which is 25.7%P higher than that of the second-best method, and yields significantly positive return rates for all stock pairs.
Laser-Assisted Etching of EagleXG Glass by Irradiation at Low Pulse-Repetition Rate
Authors: Memeo Roberto , Bertaso Mattia , Osellame Roberto , Bragheri Francesca , Crespi Andrea
Published: January 2022

Femtosecond laser micromachining is becoming an established technique for the fabrication of complex three-dimensional structures in glass. The combination of laser writing and chemical etching increases the technique versatility by allowing the fabrication of hollow structures within the bulk material. The possibility to encompass both optical and fluidic components in a single substrate allows us to realize optofluidic devices usable in several application fields. Here, we present new investigations of laser-assisted etching in Eagle XG glass showing good etching conditions at low repetition rates, where thermal effects can be neglected, and low irradiation speeds, which allow for complex microchannel network formation.
Mapping of Hydrothermal Alteration Zones in the Kelâat M’Gouna Region Using Airborne Gamma-Ray Spectrometry and Remote Sensing Data: Mining Implications (Eastern Anti-Atlas, Morocco)
Authors: Mamouch Younes , Attou Ahmed , Miftah Abdelhalim , Ouchchen Mohammed , Dadi Bouchra , Achkouch Lahsen , Et-tayea Yassine , Allaoui Abdelhamid , Boualoul Mustapha , Randazzo Giovanni , Lanza Stefania , Muzirafuti Anselme
Published: January 2022

The mapping of hydrothermal alteration zones associated with mineralization is of paramount importance in searching for metal deposits. For this purpose, targeting alteration zones by analyzing airborne geophysical and satellite imagery provides accurate and reliable results. In the Kelâat M’Gouna inlier, located in the Saghro Massif of the Moroccan Anti Atlas, natural gamma-ray spectrometry and ASTER satellite data were used to map hydrothermal alteration zones. Natural gamma-ray spectrometry data were processed to produce maps of Potassium (K in %), Uranium (eU in ppm), Thorium (eTh in ppm) and ratios of K/eTh and K/eU. In addition, four-band ratios were computed, on ASTER data, to map the distribution of clay minerals, phyllitic minerals, propylitic minerals, and iron oxides. The combined results obtained from geophysical and satellite data were further exploited by fuzzy logic modelling using the Geographic Information System (GIS) to generate a mineral prospectivity map. Seven hydrothermal alteration zones likely to be favorable for mineralization have been identified. They show a spatial correlation with (i) known surface prospects and mineral occurrences, (ii) the granite-encasing contact zone, and (iii) the fault zones (Sidi Flah and Tagmout faults). This research therefore provides important information on the prospecting of mineral potential in the study area.
Ultrasound in Telemedicine: A Brief Overview
Authors: Recker Florian , Höhne Elena , Damjanovic Domagoj , Schäfer Valentin S.
Published: January 2022

The delivery of healthcare from a distance, also known as telemedicine, has evolved over the past 50 years, changing the way healthcare is delivered globally. Its integration into numerous domains has permitted high-quality care that transcends the obstacles of geographic distance, lack of access to health care providers, and cost. Ultrasound is an effective diagnostic tool and its application within telemedicine has advanced substantially in recent years, particularly in high-income settings and low-resource areas. The literature in Pubmed from 1960–2020 was assessed with the keywords “ultrasound”, “telemedicine”, “ultrasound remote”, and “tele-ultrasound” to conduct a SWOT analysis (strengths, weaknesses, opportunities, and threats). In addressing strengths and opportunities, we emphasized practical aspects, such as the usefulness of tele-ultrasound and the cost efficiency of it. Furthermore, aspects of medical education in tele-ultrasound were considered. When it came to weaknesses and threats, we focused on issues that may not be solved immediately, and that require careful consideration or further development, such as new software that is not yet available commercially.
Potential Prebiotic and Anti-Obesity Effects of Codium fragile Extract
Authors: Oh Suwon , Kim Sungkeun , Jung Kyoojin , Pham Thi Ngoc Anh , Yang Seunghwan , Ahn Byungjae
Published: January 2022

Polysaccharides from marine algae exhibit beneficial biological activities. In this study, we examined the effect of Codium fragile extract (CFE) on prebiotic and anti-obesity activity through in vitro experiments. CFE increases the growth of specific beneficial microbial populations with concomitant decrease in pathogenic microbes. Further, total phenolic content (TPC), total flavonoid content (TFC), and DPPH radical scavenging activity (DPPH activity) after fermentation with CFE as the carbon source were higher than for glucose as the control. Moreover, CFE inhibited adipocyte differentiation by inducing differentiation-related factors when the induction of 3T3-L1 preadipocytes into adipocytes was induced. Therefore, we suggest that CFE can be used as a prebiotic material with an anti-obesity effect for human health.
Vibration Properties of Dual-Rotor Systems under Base Excitation, Mass Unbalance and Gravity
Authors: Chen Liqiang , Zeng Zhenkun , Zhang Dayi , Wang Jianjun
Published: January 2022

Rotor systems installed in a transportation system or under seismic excitations are considered to have a moving base. Although extensive research has been conducted on the dynamic behavior of the single-rotor system under base motions, few studies have dealt with the dynamics of dual-rotor systems, especially the counter-rotating dual-rotor systems used in airplane engines. Moreover, mass unbalance and gravity are unavoidable excitations for most rotor systems. Therefore, the vibration properties of a counter-rotating dual-rotor system with the coupled effects of base motions, mass unbalance and gravity are investigated in this paper for the first time. Using the Lagrange principle associated with the finite element method, a general model for dual-rotor systems under base motions was established by using Timoshenko beam elements, leading to a detailed analysis of the natural properties and harmonic responses of the system. The results revealed that different whirling modes (backward, forward or both) may be mutually excited. This research can be helpful for the design and vibration analysis of dual-rotor systems concerned with base motion.
Art and the City: Contemporary Art Galleries Districts in Paris from the End of the 19th Century until Today
Authors: Quemin Alain
Published: January 2022

The space invested by contemporary art galleries is of utmost importance. Not only is it essential to have suitable premises, but they must also be in the right place: The physical address carries a lot of weight. The benefits to galleries of being concentrated in the same areas are twofold: They are close to their competitors, which means they are close to the art market, and thus, by their collective presence, can boost the market by encouraging collectors to go to the same places built up as art districts. Moreover, the district’s qualifying function comes about through the collective construction of this grouping of galleries from which it benefits. Today in Paris, it is the Marais neighborhood—a sector that started developing in the 1970s but even more in the 1980s and 1990s—that epitomizes the place to be for contemporary art galleries. The implantation of contemporary galleries in Paris clearly results from a historical process that led them from the 8th arrondissement to the Marais, stopping briefly at Saint-Germain-des-Prés (or the 6th arrondissement) mostly for small avant-garde structures. Studying the implantation—here in Paris—of contemporary art galleries over time illustrates the dynamics that gird the installation choices and also shows how alive the urban fabric is. Galleries enter the transformations of the urban fabric, and when they are numerous enough, they also participate directly in its development.
Possible Causes of the Occurrence of a Rare Antarctic Sudden Stratospheric Warming in 2019
Authors: Ma Chenming , Yang Pengkun , Tan Xin , Bao Ming
Published: January 2022

A minor Antarctic sudden stratospheric warming (SSW) with the strongest circulation changes since the first major SSW over the Antarctic was recorded in 2002 occurred in early September 2019. The diagnosis demonstrates two possible causes of this SSW. First, the tropical central Pacific warming is identified, which enhanced the amplitude of tropospheric planetary wavenumber 1 (W1) in the extratropics on the seasonal time scale. Second, the impact of intraseasonal convection anomalies similar to previous studies is also suggested here. The enhanced deep convection over the South Pacific Convergence Zone (SPCZ) in late August–early September excited a Rossby wave train to deepen an anomalous ridge, which significantly and persistently strengthened the tropospheric W1. The central Pacific warming and intraseasonal convection anomalies jointly provided the conditions for the occurrence of the Antarctic SSW in 2019 on different time scales. On the other hand, the difference of the stratospheric state between the Antarctic SSWs in 2019 and 2002 may be an important reason why the 2019 event did not meet the major SSW criteria. The stratospheric state before the 2019 SSW event is somewhat not as ideal as that of the 2002 event. Vertical planetary waves are, hence, more difficult to enter into the polar stratosphere, making it more difficult to trigger major events.
Analysis of the Influence of Convection Heat Transfer in Circular Tubes on Ships in a Polar Environment
Authors: Yu Dongwei , Zhang Dayong , Wu Lin , Kong Xiangyi , Yue Qianjin
Published: January 2022

Electric heat tracing is the main measure for cold protection of the polar transfer coefficient in marine engineering equipment, but thermal equilibrium is the key problem this technology faces. In this paper, the circular tube was the research object. We studied the influence of convective heat transfer by Fluent software and experiments with a wind speed of 0–40 m/s and temperature of −40–0 °C by constant heat flux heating. The results show that the convective heat transfer increases with increased wind speed and decreased temperature. When the temperature is below −30 °C, the effect of temperature is increased; when the wind speed is greater than 25 m/s and the temperature is lower than −20 °C, the effect of temperature on the convective heat transfer coefficient of the circular tube increases. Based on the simulation data, we established a prediction model, and the rationality of the prediction model was verified by tests. The model provides reference for the design of electric heat tracing of circular tubes on polar ships.
Bone and Cartilage Conduction
Authors: Nishimura Tadashi
Published: January 2022

Auditory sensation is an important sensation for human beings [...]
Brain Tumor Classification Using Dense Efficient-Net
Authors: Nayak Dillip Ranjan , Padhy Neelamadhab , Mallick Pradeep Kumar , Zymbler Mikhail , Kumar Sachin
Published: January 2022

Brain tumors are most common in children and the elderly. It is a serious form of cancer caused by uncontrollable brain cell growth inside the skull. Tumor cells are notoriously difficult to classify due to their heterogeneity. Convolutional neural networks (CNNs) are the most widely used machine learning algorithm for visual learning and brain tumor recognition. This study proposed a CNN-based dense EfficientNet using min-max normalization to classify 3260 T1-weighted contrast-enhanced brain magnetic resonance images into four categories (glioma, meningioma, pituitary, and no tumor). The developed network is a variant of EfficientNet with dense and drop-out layers added. Similarly, the authors combined data augmentation with min-max normalization to increase the contrast of tumor cells. The benefit of the dense CNN model is that it can accurately categorize a limited database of pictures. As a result, the proposed approach provides exceptional overall performance. The experimental results indicate that the proposed model was 99.97% accurate during training and 98.78% accurate during testing. With high accuracy and a favorable F1 score, the newly designed EfficientNet CNN architecture can be a useful decision-making tool in the study of brain tumor diagnostic tests.
Haemodynamic Analysis of Branched Endografts for Complex Aortic Arch Repair
Authors: Sengupta Sampad , Hamady Mohamad , Xu Xiao-Yun
Published: January 2022

This study aims to investigate the haemodynamic response induced by implantation of a double-branched endograft used in thoracic endovascular aortic repair (TEVAR) of the aortic arch. Anatomically realistic models were reconstructed from CT images obtained from patients who underwent TEVAR using the RelayPlus double-branched endograft implanted in the aortic arch. Two cases (Patient 1, Patient 2) were included here, both patients presented with type A aortic dissection before TEVAR. To examine the influence of inner tunnel branch diameters on localised flow patterns, three tunnel branch diameters were tested using the geometric model reconstructed for Patient 1. Pulsatile blood flow through the models was simulated by numerically solving the Navier–Stokes equations along with a transitional flow model. The physiological boundary conditions were imposed at the model inlet and outlets, while the wall was assumed to be rigid. Our simulation results showed that the double-branched endograft allowed for the sufficient perfusion of blood to the supra-aortic branches and restored flow patterns expected in normal aortas. The diameter of tunnel branches in the device plays a crucial role in the development of flow downstream of the branches and thus must be selected carefully based on the overall geometry of the vessel. Given the importance of wall shear stress in vascular remodelling and thrombus formation, longitudinal studies should be performed in the future in order to elucidate the role of tunnel branch diameters in long-term patency of the supra-aortic branches following TEVAR with the double-branched endograft.
Increasing the Yield and Cryosurvival of Spermatozoa from Rhinoceros Ejaculates Using the Enzyme Papain
Authors: Rickard Jessica P. , Pool Kelsey , de Graaf Simon P. , Portas Timothy , Rourke Natalie , Wiesner Miriam , Hildebrandt Thomas B. , Göritz Frank , Hermes Robert
Published: January 2022

The preservation of rhinoceros semen is vital for captive breeding programs. While successful collection and cryopreservation of rhinoceros semen has been reported, the volume and quality of semen produced is often low due to the high viscosity associated with ejaculates collected via electroejaculation. Reducing semen viscosity would enable access to previously unusable spermatozoa from viscous fractions and could improve quality post-thaw. The enzyme papain successfully reduced the viscosity of camelid semen but has yet to be tested in wildlife species. This study assessed the influence of papain on the in vitro quality of rhinoceros spermatozoa during cryopreservation using advanced semen assessment. In experiment 1, the motility of spermatozoa from the viscous fraction of an ejaculate, either untreated or treated with papain and its inhibitor E-64 prior to cryopreservation, was assessed post-thaw. In experiment 2, spermatozoa from papain-treated viscous fractions were compared to spermatozoa frozen from untreated sperm-rich fractions pre-freeze, as well as after 0, 1.5 and 3 h of incubation post-thaw (37 °C). Papain significantly increased the quantity of spermatozoa collected from ejaculates, as well as the motility prior to freezing. Papain also improved the post-thaw motility, velocity, linearity and straightness of samples compared to sperm-rich samples, with no detriment to sperm viability, lipid membrane disorder, production of ROS or DNA integrity (p < 0.05). Results show the benefit of supplementing rhinoceros spermatozoa with papain prior to cryopreservation on sperm cryosurvival and demonstrates the potential of using papain to improve the success of cryopreservation protocols, not only for the rhinoceros, but also for other wildlife species.
Macrophage-like THP-1 Cells Derived from High-Density Cell Culture Are Resistant to TRAIL-Induced Cell Death via Down-Regulation of Death-Receptors DR4 and DR5
Authors: Lomovskaya Yana Vladimirovna , Kobyakova Margarita Igorevna , Senotov Anatoly Sergeevich , Lomovsky Alexey Igorevich , Minaychev Vladislav Valentinovich , Fadeeva Irina Sergeevna , Shtatnova Daria Yuryevna , Krasnov Kirill Sergeevich , Zvyagina Alena Igorevna , Akatov Vladimir Semenovich , Fadeev Roman Sergeevich
Published: January 2022

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a highly selective and promising anticancer agent due to its specific apoptosis-inducing effect on tumor cells, rather than most normal cells. TRAIL is currently under investigation for use in the treatment of leukemia. However, the resistance of leukemic cells to TRAIL-induced apoptosis may limit its efficacy. The mechanisms of leukemic cell resistance to antitumor immunity remains a topical issue. In this work, we have found an increase in the resistance to TRAIL-induced cell death in human leukemia THP-1 cells, which was caused by differentiation into a macrophage-like phenotype in high-density culture in vitro. Stressful conditions, manifested by the inhibition of cell growth and the activation of cell death in high-density culture of THP-1 cells, induced the appearance of cells adhered to culture dishes. The THP-1ad cell line was derived by selection of these adhered cells. The genetic study, using STR and aCGH assays, has shown that THP-1ad cells were derived from THP-1 cells due to mutagenesis. The THP-1ad cells possessed high proliferative potential and a macrophage-like immunophenotype. The adhesion of THP-1ad cells to the extracellular matrix was mediated by αVβ5 integrin. The cytokine production, as well as the rise of intracellular ROS and NO activities by LPS in THP-1ad cell culture, were characteristic of macrophage-like cells. The THP-1ad cells were found to appear to increase in resistance to TRAIL-induced cell death in comparison with THP-1 cells. The mechanism of the increase in TRAIL-resistance can be related to a decrease in the expression of death receptors DR4 and DR5 on the THP-1ad cells. Thus, the macrophage-like phenotype formation with the maintenance of a high proliferative potential of leukemic cells, caused by stress conditions in high-density cell cultures in vitro, can induce an increase in resistance to TRAIL-induced cell death due to the loss of DR4 and DR5 receptors. The possible realization of these events in vivo may be the reason for tumor progression.
Preparative Production of Functionalized (N- and O-Heterocyclic) Polycyclic Aromatic Hydrocarbons by Human Cytochrome P450 3A4 in a Bioreactor
Authors: Srdič Matic , Fessner Nico D. , Yildiz Deniz , Glieder Anton , Spiertz Markus , Schwaneberg Ulrich
Published: January 2022

Polycyclic aromatic hydrocarbons (PAHs) and their N- and O-containing derivatives (N-/O-PAHs) are environmental pollutants and synthetically attractive building blocks in pharmaceuticals. Functionalization of PAHs can be achieved via C-H activation by cytochrome P450 enzymes (e.g., P450 CYP3A4) in an environmentally friendly manner. Despite its broad substrate scope, the contribution of CYP3A4 to metabolize common PAHs in humans was found to be small. We recently showcased the potential of CYP3A4 in whole-cell biocatalysis with recombinant yeast Komagataella phaffii (Pichia pastoris) catalysts for the preparative-scale synthesis of naturally occurring metabolites in humans. In this study, we aimed at exploring the substrate scope of CYP3A4 towards (N-/O)-PAHs and conducted a bioconversion experiment at 10 L scale to validate the synthetic potential of CYP3A4 for the preparative-scale production of functionalized PAH metabolites. Hydroxylated products were purified and characterized using HPLC and NMR analysis. In total, 237 mg of fluorenol and 48 mg of fluorenone were produced from 498 mg of fluorene, with peak productivities of 27.7 μmol/L/h for fluorenol and 5.9 μmol/L/h for fluorenone; the latter confirmed that CYP3A4 is an excellent whole-cell biocatalyst for producing authentic human metabolites.
Neuroprotective Effects of Novel Treatments on Acute Optic Neuritis—A Meta-Analysis
Authors: Tsai Tsung-Hsien , Lin Chao-Wen , Chan Li-Wei , Tew Teck-Boon , Chen Ta-Ching
Published: January 2022

Optic neuritis, inflammation of the optic nerve, can cause visual impairment through retinal nerve fiber layer (RNFL) degeneration. Optical coherence tomography could serve as a sensitive noninvasive tool for measuring RNFL thickness and evaluating the neuroprotective effects of treatment. We conducted a meta-analysis to compare RNFL loss between novel add-on treatments and corticosteroid therapy at least 3 months after acute optic neuritis. The outcome measures were mean differences (MDs) in (1) RNFL thickness compared with the baseline in the affected and unaffected eye and (2) LogMAR visual acuity (VA). Seven studies involving five novel agents (memantine, erythropoietin, interferon-beta, phenytoin, and clemastine) were analyzed. When compared with the baseline RNFL thickness of the affected eye, the neuroprotective effects of novel add-on treatments could not be demonstrated. The difference in visual outcomes was also not significant between the two treatment groups. One study revealed that phenytoin has the potential to alleviate RNFL loss when the baseline thickness of the unaffected eye is considered. Larger randomized controlled trials with suitable outcome measures are warranted to evaluate the neuroprotective effects of novel treatments. Further studies should also tailor therapies to specific patient populations and investigate a more targeted treatment for acute optic neuritis.
Detailed Molecular Mechanisms Involved in Drug-Induced Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: An Update
Authors: Di Pasqua Laura Giuseppina , Cagna Marta , Berardo Clarissa , Vairetti Mariapia , Ferrigno Andrea
Published: January 2022

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are some of the biggest public health challenges due to their spread and increasing incidence around the world. NAFLD is characterized by intrahepatic lipid deposition, accompanied by dyslipidemia, hypertension, and insulin resistance, leading to more serious complications. Among the various causes, drug administration for the treatment of numerous kinds of diseases, such as antiarrhythmic and antihypertensive drugs, promotes the onset and progression of steatosis, causing drug-induced hepatic steatosis (DIHS). Here, we reviewed in detail the major classes of drugs that cause DIHS and the specific molecular mechanisms involved in these processes. Eight classes of drugs, among the most used for the treatment of common pathologies, were considered. The most diffused mechanism whereby drugs can induce NAFLD/NASH is interfering with mitochondrial activity, inhibiting fatty acid oxidation, but other pathways involved in lipid homeostasis are also affected. PubMed research was performed to obtain significant papers published up to November 2021. The key words included the class of drugs, or the specific compound, combined with steatosis, nonalcoholic steatohepatitis, fibrosis, fatty liver and hepatic lipid deposition. Additional information was found in the citations listed in other papers, when they were not displayed in the original search.
Multitasking Na+/Taurocholate Cotransporting Polypeptide (NTCP) as a Drug Target for HBV Infection: From Protein Engineering to Drug Discovery
Authors: Zakrzewicz Dariusz , Geyer Joachim
Published: January 2022

Hepatitis B virus (HBV) infections are among the major public health concerns worldwide with more than 250 million of chronically ill individuals. Many of them are additionally infected with the Hepatitis D virus, a satellite virus to HBV. Chronic infection frequently leads to serious liver diseases including cirrhosis and hepatocellular carcinoma, the most common type of liver cancer. Although current antiviral therapies can control HBV replication and slow down disease progress, there is an unmet medical need to identify therapies to cure this chronic infectious disease. Lately, a noteworthy progress in fighting against HBV has been made by identification of the high-affinity hepatic host receptor for HBV and HDV, namely Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1). Next to its primary function as hepatic uptake transporter for bile acids, NTCP is essential for the cellular entry of HBV and HDV into hepatocytes. Due to this high-ranking discovery, NTCP has become a valuable target for drug development strategies for HBV/HDV-infected patients. In this review, we will focus on a newly predicted three-dimensional NTCP model that was generated using computational approaches and discuss its value in understanding the NTCP’s membrane topology, substrate and virus binding taking place in plasma membranes. We will review existing data on structural, functional, and biological consequences of amino acid residue changes and mutations that lead to loss of NTCP’s transport and virus receptor functions. Finally, we will discuss new directions for future investigations aiming at development of new NTCP-based HBV entry blockers that inhibit HBV tropism in human hepatocytes.
Unveiling the Role of the Fatty Acid Binding Protein 4 in the Metabolic-Associated Fatty Liver Disease
Authors: Moreno-Vedia Juan , Girona Josefa , Ibarretxe Daiana , Masana Lluís , Rodríguez-Calvo Ricardo
Published: January 2022

Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions. Adipose tissue is the main source of liver triglycerides and adipocytes act as endocrine organs releasing a large number of adipokines and pro-inflammatory mediators involved in MAFLD progression into bloodstream. Among the adipocyte-derived molecules, fatty acid binding protein 4 (FABP4) has been recently associated with fatty liver and additional features of advanced stages of MAFLD. Additionally, emerging data from preclinical studies propose FABP4 as a causal actor involved in the disease progression, rather than a mere biomarker for the disease. Therefore, the FABP4 regulation could be considered as a potential therapeutic strategy to MAFLD. Here, we review the current knowledge of FABP4 in MAFLD, as well as its potential role as a therapeutic target for this disease.
Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database
Authors: Gavelli Francesco , Molinari Luca , Baldrighi Marco , Salmi Livia , Mearelli Filippo , Fiotti Nicola , Patrucco Filippo , Airoldi Chiara , Bellan Mattia , Sainaghi Pier Paolo , Di Somma Salvatore , Lupia Enrico , Colonetti Efrem , Muiesan Maria Lorenza , Biolo Gianni , Avanzi Gian Carlo , Castello Luigi Mario
Published: January 2022

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1–17.8] vs. 7.9 [3.8–12.9] ng/mL and 34.8 [26.4–47.5] vs. 29.8 [22.1–41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00–1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00–1.02] and 1.04 [1.02–1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00–1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02–1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.
Research Progress of Graphene and Its Derivatives towards Exhaled Breath Analysis
Authors: Yang Xinxiu , Chi Hong , Tian Yong , Li Tianduo , Wang Yaoguang
Published: January 2022

The metabolic process of the human body produces a large number of gaseous biomarkers. The tracking and monitoring of certain diseases can be achieved through the detection of these markers. Due to the superior specific surface area, large functional groups, good optical transparency, conductivity and interlayer spacing, graphene, and its derivatives are widely used in gas sensing. Herein, the development of graphene and its derivatives in gas-phase biomarker detection was reviewed in terms of the detection principle and the latest detection methods and applications in several common gases, etc. Finally, we summarized the commonly used materials, preparation methods, response mechanisms for NO, NH3, H2S, and volatile organic gas VOCs, and other gas detection, and proposed the challenges and prospective applications in this field.
Changes in Pronoun Use a Decade before Clinical Diagnosis of Alzheimer’s Dementia—Linguistic Contexts Suggest Problems in Perspective-Taking
Authors: Bittner Dagmar , Frankenberg Claudia , Schröder Johannes
Published: January 2022

The use of pronouns has been shown to change pathologically in the early phases of Alzheimer’s Dementia (AD). So far, the findings have been of a quantitative nature. Little is known, however, about the developmental path of the change, its onset, the domains in which it initially occurs, and if and how it spreads to other linguistic domains. The present study investigates pronoun use in six speakers of German a decade before they were clinically diagnosed with AD (LAD) and six biographically matched healthy controls (CTR). The data originate from monologic spoken language elicited by semi-spontaneous biographical interviews. Investigation of nine pronoun types revealed group differences in the use of three pronoun types: D-pronouns—a specific pronoun type of German for reference to persons and objects; the impersonal pronoun man ‘one’, and the propositional pronoun das ‘this/that’. Investigation of the linguistic contexts in which these three pronoun types were used revealed a correlation with declines in elaborative and evaluative information; that is, information the hearer would benefit from in creating an informed model of the discourse. We, therefore, hypothesize that the early changes in language use due to AD point to problems in perspective-taking, specifically in taking the hearer’s perspective.
Performance-Based Bi-Objective Retrofit Optimization of Building Portfolios Considering Uncertainties and Environmental Impacts
Authors: Zhou Ziyi , Anwar Ghazanfar Ali , Dong You
Published: January 2022

It is essential to assess the performance of a community under probable hazard scenarios and to provide possible performance enhancements. This requires establishing performance indicators, an assessment method, and an optimization technique to provide mitigation alternatives. In this paper, multiple performance indicators are utilized to assess the performance of a community building portfolio including loss, downtime, and environmental impact (e.g., CO2 emissions). The performance of a community is assessed by utilizing a performance-based assessment methodology. Then, the performance indicators are utilized as performance objectives to be optimized considering non-dominated sorting and crowding distance evolutionary optimization techniques. The framework utilizes retrofit alternatives for each building in a community and provides Pareto-optimal solutions for considered performance objectives given retrofit cost. This process of performance assessment and optimization is repeated by utilizing the Monte Carlo approach to consider uncertainties. Finally, the Pareto-optimal solutions are utilized to evaluate the retrofit programs for community building portfolios in terms of considered performance indicators.
Comprehensive Approach to Distinguish Patients with Solid Tumors from Healthy Controls by Combining Androgen Receptor Mutation p.H875Y with Cell-Free DNA Methylation and Circulating miRNAs
Authors: Tomeva Elena , Switzeny Olivier J. , Heitzinger Clemens , Hippe Berit , Haslberger Alexander G.
Published: January 2022

Liquid biopsy-based tests emerge progressively as an important tool for cancer diagnostics and management. Currently, researchers focus on a single biomarker type and one tumor entity. This study aimed to create a multi-analyte liquid biopsy test for the simultaneous detection of several solid cancers. For this purpose, we analyzed cell-free DNA (cfDNA) mutations and methylation, as well as circulating miRNAs (miRNAs) in plasma samples from 97 patients with cancer (20 bladder, 9 brain, 30 breast, 28 colorectal, 29 lung, 19 ovarian, 12 pancreas, 27 prostate, 23 stomach) and 15 healthy controls via real-time qPCR. Androgen receptor p.H875Y mutation (AR) was detected for the first time in bladder, lung, stomach, ovarian, brain, and pancreas cancer, all together in 51.3% of all cancer samples and in none of the healthy controls. A discriminant function model, comprising cfDNA mutations (COSM10758, COSM18561), cfDNA methylation markers (MLH1, MDR1, GATA5, SFN) and miRNAs (miR-17-5p, miR-20a-5p, miR-21-5p, miR-26a-5p, miR-27a-3p, miR-29c-3p, miR-92a-3p, miR-101-3p, miR-133a-3p, miR-148b-3p, miR-155-5p, miR-195-5p) could further classify healthy and tumor samples with 95.4% accuracy, 97.9% sensitivity, 80% specificity. This multi-analyte liquid biopsy-based test may help improve the simultaneous detection of several cancer types and underlines the importance of combining genetic and epigenetic biomarkers.
c-Myc Targets HDAC3 to Suppress NKG2DL Expression and Innate Immune Response in N-Type SCLC through Histone Deacetylation
Authors: Zhao Peiyan , Sun Xiaodan , Li Hui , Liu Yan , Cui Yanan , Tian Lin , Cheng Ying
Published: January 2022

SCLC is an aggressive malignancy with a very poor prognosis and limited effective therapeutic options. Despite the high tumor mutational burden, responses to immunotherapy are rare in SCLC patients, which may be due to the lack of immune surveillance. Here, we aimed to examine the role and mechanism of oncogene MYC in the regulation of NKG2DL, the most relevant NK-activating ligand in SCLC-N. Western Blotting, Immunofluorescence, flow cytometry, quantitative real-time PCR (qRT-PCR), Co-Immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and Cytotoxicity assay were used on H2227 cells, H446 cells, and other SCLC cell lines, and we found that c-Myc negatively regulated NKG2DL expression in SCLC-N cells. Mechanistically, c-Myc recruited HDAC3 to deacetylate H3K9ac at the promoter regions of MICA and MICB, suppressing the MICA/B expression of SCLC-N cells and the cytotoxicity of NK cells. Treatment with selective HDAC3 inhibitor up-regulated the expression of NKG2DL on SCLC-N cells and increased the cytotoxicity of NK cells. Furthermore, analysis of the CCLE and Kaplan-Meier plotter data performed the negative correlation between MYC and NKG2DL in SCLC-N cells and the correlation with the prognosis of lung cancer patients. Collectively, the results provided the new insight into the role and mechanism of c-Myc/HDAC3 axis in NKG2DL expression and innate immune escape of SCLC-N, suggesting the potential target for SCLC-N immunotherapy.
Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors
Authors: Macagno Nicolas , Sohier Pierre , Kervarrec Thibault , Pissaloux Daniel , Jullie Marie-Laure , Cribier Bernard , Battistella Maxime
Published: January 2022

Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex terminology make their pathological diagnosis challenging. Recent findings have revealed a wide spectrum of oncogenic drivers, several of which are of diagnostic interest for pathologists. Most of these molecular alterations are represented by gene fusions, which are shared with other homologous neoplasms occurring in organs containing exocrine glands, such as salivary and breast glands, which show similarities to the sweat apparatus. This review aims to provide a synthesis of the most recent immunohistochemical and molecular markers used for the diagnosis of sweat gland tumors and to highlight their relationship with similar tumors in other organs. It will cover adenoid cystic carcinoma (NFIB, MYB, and MYBL1 fusion), cutaneous mixed tumor (PLAG1 fusion), cylindroma and spiradenoma and their carcinomas thereof (NF-κB activation through CYLD inactivation or ALKP1 hotspot mutation), hidradenoma and hidradenocarcinoma (MAML2 fusion), myoepithelioma (EWSR1 and FUS fusion), poroma and porocarcinoma (YAP1, MAML2, and NUTM1 fusion), secretory carcinoma (ETV6, NTRK3 fusion), tubular adenoma and syringo-cystadenoma papilliferum (HRAS and BRAF activating mutations). Sweat gland tumors for which there are no known molecular abnormalities will also be briefly discussed, as well as potential future developments.
Co and Ni Incorporated γ-Al2O3 (110) Surface: A Density Functional Theory Study
Authors: Li Huaxi , Shi Liu , Jin Chengkai , Ye Runping , Zhang Rongbin
Published: January 2022

Investigation into the state and mechanisms of the active metal substitution into the γ-Al2O3 support is the basis for design of many catalysts. Periodic density functional theory (DFT) +U calculations were used to investigate the surface properties of transition metals Co3+ and Ni3+ cations substitute for the Al3+ cations of γ-Al2O3 (110) surface. It was found that the substitution energy of one Al3+ substituted by Co3+ and Ni3+ are −61 and −57 kJ/mol, respectively. The Co and Ni preferentially substitute the tetrahedral Al sites instead of the octahedral Al sites. Using thermodynamics, the Al atoms in the top layer of γ-Al2O3 (110) can be 100% substituted by Co and Ni. Ni is easier to substitute the Al atom than Co. There is no obvious structural distortion that occurs after Co and Ni substituted all the top layer Al atoms. While the band gaps of the substituted surface become narrower, resulting in the increase of surface Lewis acidity. In addition, the oxygen vacancy formation energies of the Co and Ni substituted surface are 268 and 53 kJ/mol, respectively. The results provide interface structure and physical chemistry properties of metal-doped catalysts.