bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Dietary Lavender Essential Oil on the Growth and Fatty Acid Profile of Breast Muscles, Antioxidant Activity, and Inflammatory Responses in Broiler Chickens
Authors: Amer Shimaa A. , Abdel-Wareth Ahmed A. A. , Gouda Ahmed , Saleh Gehan K. , Nassar Arwa H. , Sherief Wafaa R. I. A. , Albogami Sarah , Shalaby Shimaa I. , Abdelazim Aaser M. , Abomughaid Mosleh Mohammad
Published: September 2022

This study aimed to investigate the impact of dietary addition of lavender essential oil (Lavandula angustifolia L.) (LEO) on the growth performance, tissue histoarchitecture, and fatty acid profile in breast muscles, as well as blood biochemistry and immune expression of pro-inflammatory cytokines of broiler chickens. A total of 200 three-day-old broiler chickens (average body weight 101.3 ± 0.24 g) were assigned to a completely randomized design consisting of four dietary treatments (n = 50 per treatment, each replicate consisting of 10 birds) that included lavender essential oil at concentrations of 0 (control group), 200, 400, and 600 mg Kg−1 diet. The experiment lasted for 35 days. The results revealed that supplementation of lavender essential oil at 200, 400, or 600 mg/kg in broiler diets had no effect (p > 0.05) on the growth performance throughout the experimental periods (3–10, 11–23, and 24–35 days of age). According to the broken line regression model, the optimal level for dietary LEO addition was the 460 mg kg−1 diet based on the total body weight gain and feed conversion ratio results. The diets supplemented with lavender essential oil had no effect (p > 0.05) on the percentages of carcass yield or internal organs. Dietary addition of LEO significantly increased the percentages of omega-3 polyunsaturated fatty acids PUFA (n-3), omega-6 polyunsaturated fatty acids (n-6), and the n-3/n-6 ratio (p < 0.05) in the breast muscles of chickens in a level-dependent manner. The blood concentration of alanine aminotransferase was significantly increased in lavender essential oil at 600 mg kg−1 compared with other treatments. The dietary addition of LEO at 200, 400, and 600 mg kg−1 significantly reduced the malondialdehyde level. Still, they significantly increased the serum enzyme activities of total antioxidant capacity, catalase, superoxide dismutase, and the pro-inflammatory cytokine (interleukine-1 beta and interferon γ) compared with the unsupplemented group. The LEO-supplemented groups showed normal liver histomorphology as in the control group. However, the immunoexpression of the pro-inflammatory cytokine transforming growth factor β was significantly increased by increasing the level of LEO. It can be concluded that lavender essential oil can be included in broiler chicken diets up to 460 mg kg −1 with no positive effect on the bird’s growth. It can improve the antioxidant capacity and enrich the breast muscles with PUFA. An increased level of supplementation (600 mg kg−1) increased the inflammatory responses in broiler chickens.
Functionalized Carbon-Based Electrochemical Sensors for Food and Alcoholic Beverage Safety
Authors: Yang Zhongjie , Zhang Xiaofei , Guo Jun
Published: September 2022

Food is a necessity in people’s lives. Equally importantly, alcoholic beverages are also highly demanded globally due to the indispensable role they play in cultural, social, and ritual events. However, the production of food and alcoholic beverages suffers from a variety of contaminants, such as toxins, pesticides, antibiotic residues, and heavy metals, which are seriously harmful to human beings. These urgent threats have raised the awareness of the need to improve product quality and safety via developing effective, rapid, and economical monitoring and detecting methods. Fortunately, due to their numerous advantages, including high sensitivity, short response time, low cost, and easy portability, electrochemistry sensors have made huge contributions to ensuring the quality of food and alcoholic beverages. The purpose of this review is to introduce applications of electrochemical sensors to foods and alcoholic beverages, and to highlight the important role of carbon-based materials (i.e., carbon dots, carbon nanotubes, and graphene) as electrochemical sensors in detecting various contaminants. In addition, the preparation methods of these carbon-based electrochemical sensors and corresponding detection mechanisms are discussed in detail. It is hoped that this review can inspire more innovative detection technologies for ensuring the safety of food and alcoholic beverages.
An Investigation on the Synthesis of Alkali Activated Materials from Thermally Modified Clays
Authors: Ascensão Guilherme , Bernardo Enrico , Ferreira Victor M.
Published: September 2022

The sustainability and economic competitiveness of alkali activation technology greatly depends on expanding the raw materials database with locally available resources. Therefore, a notable trend has been witnessed toward the exploitation of common clays as alternatives to well-established solid aluminosilicate precursors due to their availability and wide geographical distribution. However, common clays are complex and dedicated research is needed to tailor synthesis procedures and mix designs for different clay resources. This paper describes the outcomes of a study conducted to investigate the influence of several synthesis parameters (solid-to-liquid ratio, NaOH molarity, Si availability, and curing conditions) on the properties of alkali activated binders produced from different thermally modified clays. Optimal synthesis conditions for benchmark metakaolin systems have been identified and binders were produced with progressive dosages of metakaolin replacement by common local clays. Fundamental physical and mechanical properties such as apparent density, open porosity, water absorption, and compressive strength were examined at different curing ages, and X-ray diffraction (XRD) was used to provide complementary mineralogical insights. By combining the effects of the parameters studied, mortar specimens were produced with the developed binders, reaching compressive strength values exceeding 28.2 ± 0.1 MPa, a bulk density as low as 1.78 ± 0.0 g/cm3, and open porosity and water absorption values lower than 15% and 8%, respectively. These properties are comparable to those of conventional hydraulic products, which presents them as interesting candidates for construction. Ultimately, this work aims to contribute with valuable insights toward the valorization of a large group of unexploited clay precursors by demonstrating the feasibility of producing technologically competitive alkali activated materials with little or no use of the prime precursors, thus adding to the extant knowledge and contributing to future scientific and industrial developments in this field.
Process-Oriented Stream Classification Pipeline: A Literature Review
Authors: Clever Lena , Pohl Janina Susanne , Bossek Jakob , Kerschke Pascal , Trautmann Heike
Published: September 2022

Due to the rise of continuous data-generating applications, analyzing data streams has gained increasing attention over the past decades. A core research area in stream data is stream classification, which categorizes or detects data points within an evolving stream of observations. Areas of stream classification are diverse—ranging, e.g., from monitoring sensor data to analyzing a wide range of (social) media applications. Research in stream classification is related to developing methods that adapt to the changing and potentially volatile data stream. It focuses on individual aspects of the stream classification pipeline, e.g., designing suitable algorithm architectures, an efficient train and test procedure, or detecting so-called concept drifts. As a result of the many different research questions and strands, the field is challenging to grasp, especially for beginners. This survey explores, summarizes, and categorizes work within the domain of stream classification and identifies core research threads over the past few years. It is structured based on the stream classification process to facilitate coordination within this complex topic, including common application scenarios and benchmarking data sets. Thus, both newcomers to the field and experts who want to widen their scope can gain (additional) insight into this research area and find starting points and pointers to more in-depth literature on specific issues and research directions in the field.
Track–Bridge Interaction of CWR on Chinese Large-Span Bridge of High-Speed Railway
Authors: Yan Bin , Kuang Wenfei , Gan Rui , Xie Haoran , Huang Jie
Published: September 2022

The track–bridge interaction is a fundamental concern in the field of railway engineering, which plays an important role in the optimization design of railway bridges, especially for heavy-haul railway and high-speed railway bridges. This paper systematically introduces the research status of the CWR track–bridge interaction for large-span bridges of high-speed railway in China. The evolution process of the track–bridge interaction model from the simplest elastic bar and linear longitudinal resistance model to the complex beam–rail interaction model considering the loading history is described. In this paper, the modeling methods of the track–bridge interaction model for five types of long-span railway bridges, namely simply supported beam bridge, continuous beam bridge, cable-stayed bridge, arch bridge, and suspension bridge, are systematically introduced, and the characteristics of longitudinal force distribution under the track–bridge interaction are analyzed. This paper discusses the practical application of the theory of the track–bridge interaction on extra-large-span bridges from the aspects of system dynamic performance evaluation and system safety evaluation. The practical application of track–bridge interaction theory under special conditions such as earthquake load, complex temperature load, shrinkage and creep load, and superposition of multiple loads is emphasized. It provides guidance for the further improvement of the track–bridge interaction model and the design of large-span high-speed railway bridges in the future.
Adaptive Control of Flapping-Wing Micro Aerial Vehicle with Coupled Dynamics and Unknown Model Parameters
Authors: Mou Jiawang , Zhang Weiping , Wu Chaofeng , Guo Qingcheng
Published: September 2022

With the complex aerodynamics, the accurate system model of the flapping-wing micro aerial vehicle required for precise control is hard to acquire, meanwhile, due to the unique control strategy, the coupling between the actuators also brings a great challenge to the control of the vehicle. In this paper, we establish a theoretical model of the vehicle. Based on this model, we propose a multiaxial adaptive controller with the reference generator for the attitude and altitude control using the backstepping design method, the stability of this controller is proved by the Lyapunov function. Moreover, a control allocation algorithm is proposed to coordinate the different actuators such that they together produce the desired virtual control efforts. In addition, we detail the lightweight design of the flapping-wing micro aerial vehicle with altitude and attitude sensing onboard. Then, the effectiveness of the proposed control scheme is verified by the simulation and the flight test with multi-axis simultaneous control conducted on this lightweight vehicle. The experimental results show that the controller can maintain hovering flight and ensure the convergence of the adaptive parameters even when the unilateral thrust of the vehicle is not enough due to manufacturing and assembly errors. This work provides an idea for us to explore how insects maintain stable flight in the face of changes in their model parameters.
Experimental Volume Incidence Study and the Relationship of Polypropylene Macrofiber Slenderness to the Mechanical Strengths of Fiber-Reinforced Concretes
Authors: Almeida Del Savio Alexandre , La Torre Darwin , Cedrón Juan P.
Published: September 2022

An experimental study was conducted to examine the mechanical strengths of concretes with straight high-strength knurled polypropylene macrofibers. Incidences of concrete mechanical strengths were determined for three different fiber dosages and lengths. In addition, compressive, indirect-splitting-test tensile, and flexural strengths were determined through testing. The results showed no statistically significant correlation between the volume and length of fibers with the compressive strength of polypropylene fiber-reinforced concrete (PPFRC). However, there was a statistically significant correlation between the split tensile strength, the volume, and the length of the fibers when the volume was greater than 0.80%, and the length of the fibers was greater than 50 mm. Furthermore, the modulus of rupture increased when the volume of fibers was greater than 0.80% and the length of the fibers was 60 mm. Finally, equations were proposed to determine the tensile strength by split test and the modulus of rupture as a function of the mixture’s resistance without fibers, the fibers’ volume and length.
Mid-Infrared Highly Efficient, Broadband, and Flattened Dispersive Wave Generation via Dual-Coupled Thin-Film Lithium-Niobate-on-Insulator Waveguide
Authors: Jia Jing , Kang Zhe , Huang Qiangsheng , He Sailing
Published: September 2022

We designed a structure of dual-coupled ridge waveguide in thin-film lithium-niobate-on-insulator (LNOI) and numerically studied the highly efficient, broadband, and flattened dispersive wave-enhanced supercontinuum generation in the mid-infrared region. By leveraging the mode coupling of the proposed dual-coupled waveguide structure, one of the supermodes, namely the anti-symmetric mode, can produce additional zero-dispersion wavelengths in the mid-infrared region, and consequently multiple normal dispersion regions for dispersive wave emission. Given the rich geometrical degrees of freedom powered by this dual-coupled LNOI waveguide structure, we can tailor the dispersion profile so that a well-established mode-locked fiber laser in the telecommunication band can serve as the pump. Thus, the whole system can potentially be fiber-to-chip integrated and packaged, enabling a compact, cost-effective, and low system-complexity platform. We numerically show that the broadband dispersive wave covering the wavelength range of 1.92~3.55 μm (−20 dB level, near octave-spanning) with spectral flatness of 6.31 dB can be achieved using a 1550 nm, 190 pJ femtosecond pump seed. When the dual hump-shaped spectrum is obtained, the conversion efficiency of the mid-infrared dispersive wave can be up to 19.31%. The influence of the pumping conditions on the performance of mid-infrared dispersive wave generation was also studied. This work provides a competitive candidate for efficient, broadband, and flattened mid-infrared spectrum generation, which can find important applications in spectroscopy, metrology, and communication.
Hybrid Modeling for Solutions of Sediment Deposition in a Low-Land Reservoir with Multigate Sluice Structure
Authors: Xie Qiancheng , Yang James , Lundström T. Staffan , Chen Jieren
Published: September 2022

At the multigate sluice structure on a fluvial river, undesired sediment deposition affects the normal operation of the reservoir in question. Physical and numerical models are hybridized to help explore flow and sedimentation patterns. Field and laboratory investigations show that the deposition is attributable to the formation of large recirculation zones at low and medium discharges. As a potential countermeasure, an array of guide vanes is recommended to cope with the concern. Their attack angle with the flow is a dominant parameter that needs to be evaluated. Tests in the fixed-bed model demonstrate that the vanes bend the reservoir flow towards the sluice and suppress the circulation zones along both banks. The favorable range of attack angle is 15–20°. With the examination of sedimentation of both bed and suspended loads, the numerical modeling indicates that the sediment-removal efficiency increases with an increase in attack angle. By weighing the flushing efficiency and the risk of local scouring at the vanes, the 15° vane layout is recommended. This study is expected to provide a reference for guide-vane design in similar situations.
Electron-Impact Ionization of the Tungsten Ions: W38+ − W45+
Authors: Bao Runjia , Wei Junkui , Li Bowen , Chen Ximeng
Published: September 2022

In this manuscript, we present our calculations of detailed electron-impact single ionization cross-sections for tungsten ions, spanning charge states W38+− W45+. The level-to-level distorted-wave method implemented in the flexible atomic code (FAC) was used for calculation. Comparison between the present level-to-level distorted wave treatment and previous configuration-averaged calculations has been performed for the W45+ ion, and we explore the possible reason for the difference observed between two calculations. We demonstrate the importance of radiative damping on the total electron-impact ionization cross-section for the W43+ ion. Present calculations provide missing cross-sections for W38+− W45+. The data obtained are expected to be useful for modeling plasmas for fusion applications, especially for the ITER community.
Procedure for Assessing the Suitability of Battery Second Life Applications after EV First Life
Authors: Montes Tomás , Etxandi-Santolaya Maite , Eichman Josh , Ferreira Victor José , Trilla Lluís , Corchero Cristina
Published: September 2022

Using batteries after their first life in an Electric Vehicle (EV) represents an opportunity to reduce the environmental impact and increase the economic benefits before recycling the battery. Many different second life applications have been proposed, each with multiple criteria that have to be taken into consideration when deciding the most suitable course of action. In this article, a battery assessment procedure is proposed that consolidates and expands upon the approaches in the literature, and facilitates the decision-making process for a battery after it has reached the end of its first life. The procedure is composed of three stages, including an evaluation of the state of the battery, an evaluation of the technical viability and an economic evaluation. Options for battery configurations are explored (pack direct use, stack of battery packs, module direct use, pack refurbish with modules, pack refurbish with cells). By comparing these configurations with the technical requirements for second life applications, a reader can rapidly understand the tradeoffs and practical strategies for how best to implement second life batteries for their specific application. Lastly, an economic evaluation process is developed to determine the cost of implementing various second life battery configurations and the revenue for different end use applications. An example of the battery assessment procedure is included to demonstrate how it could be carried out.
Glycocalyx Sensing with a Mathematical Model of Acoustic Shear Wave Biosensor
Authors: Turova Varvara , Kovtanyuk Andrey , Pykhteev Oleg , Sidorenko Irina , Lampe Renée
Published: September 2022

The article deals with an idea of exploiting an acoustic shear wave biosensor for investigating the glycocalyx, a polysaccharide polymer molecule layer on the endothelium of blood vessels that, according to recent studies, plays an important role in protecting against diseases. To test this idea, a mathematical model of an acoustic shear wave sensor and corresponding software developed earlier for proteomic applications are used. In this case, the glycocalyx is treated as a layer homogenized over the thin polymer “villi”. Its material characteristics depend on the density, thickness, and length of the villi and on the viscous properties of the surrounding liquid (blood plasma). It is proved that the model used has a good sensitivity to the above parameters of the villi and blood plasma. Numerical experiments performed using real data collected retrospectively from premature infants show that the use of acoustic shear wave sensors may be a promising approach to investigate properties of glycocalyx-like structures and their role in prematurity.
All Trans-Retinoic Acids Facilitate the Remodeling of 2D and 3D Cultured Human Conjunctival Fibroblasts
Authors: Tsugeno Yuri , Sato Tatsuya , Watanabe Megumi , Higashide Megumi , Furuhashi Masato , Umetsu Araya , Suzuki Soma , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: September 2022

Vitamin A derivative, all-trans-retinoic acid (ATRA), is known to be a potent regulator of the growth and differentiation of various types of cells. In the present study, the unidentified effects of ATRA on superficial and vertical spreading conjunctival scarring were examined. The study involved the use of two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblast (HconF) cells in the presence or absence of TGF-β2. The effects of ATRA (1 μM) on superficial or vertical spreading conjunctival scarring were evaluated by the barrier function by trans-endothelial electrical resistance (TEER) and FITC dextran permeability measurements and real-time metabolic analysis, as well as the physical properties, namely, the size and stiffness, of 3D spheroids, respectively. In addition, the expressions of several related molecules, including extracellular matrix (ECM) molecules, ECM modulators including a tissue inhibitor of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and ER stress-related factors, were examined. ATRA significantly induced (1) an increase in TEER values and a decrease in FITC dextran permeability, respectively, in the 2D monolayers, and (2) relatively and substantially increased the size and stiffness, respectively, of the 3D spheroids. These ATRA-induced effects were further enhanced in the TGF-β2-treated cells, whereas the TGF-β2-induced enhancement in glycolytic capacity was canceled by the presence of ATRA. Consistent with these physical and morphological effects, the mRNA expressions of several molecules were significantly but differently induced between 2D and 3D cultures by ATRA, although the presence of TGF-β2 did not substantially affect these gene expression levels. The findings reported in this study indicate that ATRA may exacerbate both superficial and vertical conjunctival fibrosis spreading independently of TGF-β2-induced changes.
Evaluation of a Locking Autocompression Screw Model in Pauwels Type-3 Femoral Neck Fracture: In Vitro Analysis
Authors: Giordano Vincenzo , Freitas Anderson , Pires Robinson Esteves , Battaglion Leonardo Rigobello , Lobo Mariana de Oliveira , Belangero William Dias
Published: September 2022

Femoral neck fractures in young adults are uncommon, resulting from high-energy trauma. Despite their infrequency in this population, there is higher rate of complications, especially in the more vertical fracture line, classified by Pauwels as a type-3 femoral neck fracture. The implant type is of paramount importance for maintaining anatomical reduction, since it must resist the deforming forces that act on the fracture. We comparatively evaluated two constructions of the novel locking autocompression implant (X-PIN and X-PIN+P) using the finite element method and previously established methods for treating Pauwels type-3 femoral neck fractures. Six fixation models were developed for the study: a dynamic hip screw (DHS), a DHS with an anti-rotation screw (DHS+P), the inverted triangle multiple cannulated screws construction (ASNIS), the multiple cannulated screws in an L-configuration (L), and the two models of the novel locking autocompression screw (X-PIN and X-PIN+P). Under the same conditions with a load of 2100 N, the following parameters were evaluated using SIMLAB® software: the main maximum (Max P), main minimum (Min P), localized maximum P1 (Max P1), localized maximum P2 (Max P2), total displacement, localized displacement, rotation displacement, and von Mises stress. Compared to the DHS+P and ASNIS models, the X-PIN+P model presented, respectively, increases of 51.6% and 64.7% for Max P, 85% and 247% for Min P, and 18.9% and 166.7% for von Mises stress. Max P1 did not differ between the models, but Max P2 was 55% and 50% lower for X-PIN+P than ASNIS and L, respectively. All displacement values were lower for X-PIN+P than the other models. In this FEM testing, the X-PIN+P was superior to the other models, which was due to improvement in all parameters of stress distribution, displacement, and von Mises stress compared to models using a lateral plate (DHS and DHS+P) or not (ASNIS and L).
The Ni(II)-Binding Activity of the Intrinsically Disordered Region of Human NDRG1, a Protein Involved in Cancer Development
Authors: Beniamino Ylenia , Cenni Vittoria , Piccioli Mario , Ciurli Stefano , Zambelli Barbara
Published: September 2022

Nickel exposure is associated with tumors of the respiratory tract such as lung and nasal cancers, acting through still-uncharacterized mechanisms. Understanding the molecular basis of nickel-induced carcinogenesis requires unraveling the mode and the effects of Ni(II) binding to its intracellular targets. A possible Ni(II)-binding protein and a potential focus for cancer treatment is hNDRG1, a protein induced by Ni(II) through the hypoxia response pathway, whose expression correlates with higher cancer aggressiveness and resistance to chemotherapy in lung tissue. The protein sequence contains a unique C-terminal sequence of 83 residues (hNDRG1*C), featuring a three-times-repeated decapeptide, involved in metal binding, lipid interaction and post-translational phosphorylation. In the present work, the biochemical and biophysical characterization of unmodified hNDRG1*C was performed. Bioinformatic analysis assigned it to the family of the intrinsically disordered regions and the absence of secondary and tertiary structure was experimentally proven by circular dichroism and NMR. Isothermal titration calorimetry revealed the occurrence of a Ni(II)-binding event with micromolar affinity. Detailed information on the Ni(II)-binding site and on the residues involved was obtained in an extensive NMR study, revealing an octahedral paramagnetic metal coordination that does not cause any major change of the protein backbone, which is coherent with CD analysis. hNDRG1*C was found in a monomeric form by light-scattering experiments, while the full-length hNDRG1 monomer was found in equilibrium between the dimer and tetramer, both in solution and in human cell lines. The results are the first essential step for understanding the cellular function of hNDRG1*C at the molecular level, with potential future applications to clarify its role and the role of Ni(II) in cancer development.
Integrating Text Mining into the Curation of Disease Maps
Authors: Voskamp Malte , Vinhoven Liza , Stanke Frauke , Hafkemeyer Sylvia , Nietert Manuel Manfred
Published: September 2022

An adequate visualization form is required to gain an overview and ultimately understand the complex and diverse biological mechanisms of diseases. Recently, disease maps have been introduced for this purpose. A disease map is defined as a systems biological map or model that combines metabolic, signaling, and physiological pathways to create a comprehensive overview of known disease mechanisms. With the increase in publications describing biological interactions, efforts in creating and curating comprehensive disease maps is growing accordingly. Therefore, new computational approaches are needed to reduce the time that manual curation takes. Test mining algorithms can be used to analyse the natural language of scientific publications. These types of algorithms can take humanly readable text passages and convert them into a more ordered, machine-usable data structure. To support the creation of disease maps by text mining, we developed an interactive, user-friendly disease map viewer. The disease map viewer displays text mining results in a systems biology map, where the user can review them and either validate or reject identified interactions. Ultimately, the viewer brings together the time-saving advantages of text mining with the accuracy of manual data curation.
Enzymatic Potential of Filamentous Fungi as a Biological Pretreatment for Acidogenic Fermentation of Coffee Waste
Authors: Pereira Joana , Cachinho Ana , de Melo Marcelo M. R. , Silva Carlos M. , Lemos Paulo C. , Xavier Ana M. R. B. , Serafim Luísa S.
Published: September 2022

Spent coffee grounds (SCGs) are a promising substrate that can be valorized by biotechnological processes, such as for short-chain organic acid (SCOA) production, but their complex structure implies the application of a pretreatment step to increase their biodegradability. Physicochemical pretreatments are widely studied but have multiple drawbacks. An alternative is the application of biological pretreatments that include using fungi Trametes versicolor and Paecilomyces variotii that naturally can degrade complex substrates such as SCGs. This study intended to compare acidic and basic hydrolysis and supercritical CO2 extraction with the application of these fungi. The highest concentration of SCOAs, 2.52 gCOD/L, was achieved after the acidification of SCGs pretreated with acid hydrolysis, but a very similar result, 2.44 gCOD/L, was obtained after submerged fermentation of SCGs by T. versicolor. This pretreatment also resulted in the best acidification degree, 48%, a very promising result compared to the 13% obtained with the control, untreated SCGs, highlighting the potential of biological pretreatments.
Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma after Discontinuing Pembrolizumab as a Second-Line Treatment: A Retrospective Multicenter Real-World Cohort Study
Authors: Yamada Toyohiro , Nakane Keita , Enomoto Torai , Tomioka Masayuki , Taniguchi Tomoki , Ishida Takashi , Ozawa Kaori , Takagi Kimiaki , Ito Hiroki , Takeuchi Shinichi , Kawase Makoto , Kawase Kota , Kato Daiki , Takai Manabu , Iinuma Koji , Yokoi Shigeaki , Nakano Masahiro , Koie Takuya
Published: September 2022

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.
Level of Potassium Is Associated with Saturated Fatty Acids in Cell Membranes and Influences the Activation of the 9 and 13 HODE and 5 HETE Synthesis Pathways in PCOS
Authors: Szczuko Małgorzata , Pokorska-Niewiada Kamila , Kwiatkowska Lidia , Nawrocka-Rutkowska Jolanta , Szydłowska Iwona , Ziętek Maciej
Published: September 2022

Potassium helps to maintain the water–electrolyte and acid–base balance. There is little research on the relationship between plasma fatty acids (FAs), inflammatory mediators and red blood cell potassium levels in women with polycystic ovary syndrome (PCOS). This study included 38 Caucasian women with PCOS. Potassium in the erythrocytes was determined by inductively coupled atomic plasma emission spectrometry. The FAs were analysed with gas chromatography, and liquid chromatography was used to separate the eicosanoids. The relationships between the potassium content and the amounts of fatty acids, as well as potassium and arachidonic acid (AAs) derivatives, were analysed. Significant negative correlations were found with, among others, pentadecanoic acid, palmitic acid, stearic acid and arachidic acid, whereas a positive correlation was found with neuronic acid. Positive correlations were observed with 9, 13 HODE (derivatives synthetized from linolenic acid) and 5 oxo ETE and 5 HETE (from 5 LOX pathway). Saturated fatty acids reduce the influx of potassium into the cell by destabilizing the pH of the cytosol, and thus exacerbating the inflammatory response through the activation of the AA cascade. Therefore, improving the flow of potassium inside the cell is important in the treatment of patients.
GJA1/CX43 High Expression Levels in the Cervical Spinal Cord of ALS Patients Correlate to Microglia-Mediated Neuroinflammatory Profile
Authors: Vicario Nunzio , Castrogiovanni Paola , Imbesi Rosa , Giallongo Sebastiano , Mannino Giuliana , Furno Debora Lo , Giuffrida Rosario , Zappalà Agata , Li Volti Giovanni , Tibullo Daniele , Di Rosa Michelino , Parenti Rosalba
Published: September 2022

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motoneurons (MNs) with a fatal outcome. The typical degeneration of cortico-spinal, spinal, and bulbar MNs, observed in post-mortem biopsies, is associated with the activation of neuroimmune cells. GJA1, a member of the connexins (Cxs) gene family, encodes for connexin 43 (Cx43), a core gap junctions (GJs)- and hemichannels (HCs)-forming protein, involved in cell death, proliferation, and differentiation. Recently, Cx43 expression was found to play a role in ALS pathogenesis. Here, we used microarray and RNA-seq datasets from the NCBI of the spinal cord of control (NDC) and ALS patients, which were stratified according to the GJA1 gene expression. Genes that positively or negatively correlated to GJA1 expression were used to perform a genomic deconvolution analysis (GDA) using neuroimmune signatures. Expression analysis revealed a significantly higher GJA1 expression in the MNs of ALS patients as compared to NDC. Gene deconvolution analysis revealed that positively correlated genes were associated with microglia activation, whereas negatively correlated genes were associated with neuronal activation profiles. Moreover, gene ontology analysis, performed on genes characterizing either microglia or neuronal signature, indicated immune activation or neurogenesis as main biological processes. Finally, using a synthetic analysis of drugs able to revert the GJA1 transcriptomic signatures, we found a specific drug profile for ALS patients with high GJA1 expression levels, composed of amlodipine, sertraline, and prednisolone. In conclusion, our exploratory study suggests GJA1 as a new neuro-immunological gene correlated to microglial cellular profile in the spinal cord of ALS patients. Further studies are warranted to confirm these results and to evaluate the therapeutic potential of drugs able to revert typical GJA1/CX43 signature in ALS patients
Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis
Authors: Wu Liusheng , Zhong Yanfeng , Wu Dingwang , Xu Pengcheng , Ruan Xin , Yan Jun , Liu Jixian , Li Xiaoqiang
Published: September 2022

[Objective] Using multi-omics research methods to explore cytolytic activity-related genes through the immunoregulatory factors HAVCR2 (TIM3) affecting the survival and prognosis of lung adenocarcinoma. [Methods] We combined Cox single factor regression and lasso regression feature selection algorithm to screen out the key genes of cytolytic activity in lung adenocarcinoma, and applied multi-omics research to explore the clinical predictive value of the model, including onset risk, independent prognosis, clinical relevance, signal transduction pathways, drug sensitivity, and the correlation of immune regulatory factors, etc. TCGA data are used as the experimental group, and GEO data is used as the external data control group to verify the stability of the model. The survival curve was generated by the Kaplan–Meier method and compared by log-rank, and the Cox proportional hazard model was used for multivariate analysis. In this study, 10 fresh tissue samples of lung adenocarcinoma were collected for cellular immunohistochemical experiments to analyze the expression of immunoregulatory factors in cancer tissues, and the key immunoregulatory factors were verified and screened out. [Results] A total of 450 genes related to cytolytic activity were differentially expressed, of which 273 genes were up-regulated and 177 genes were down-regulated. A total of 91 key genes related to cytolytic activity related to the prognosis of lung adenocarcinoma were screened through Cox single factor regression. The ROC curve results showed that the AUC values of 1, 3, and 5 years in the training set and test set were all greater than 0.7, indicating that the model has a valid verification. The level of risk score is significantly related to the sensitivity of patients to AKT inhibitor VIII, Lenalidomide, and Tipifarnib. In addition, our study also found that receptor and MHC genes related to immunomodulatory, and chemokines, including HAVCR2, are more highly expressed in the low-risk group. [Conclusions] HAVCR2 (TIM3) immunoregulatory factors affect the expression of key genes that affect cytolytic activity in lung adenocarcinoma cells, and to some extent indirectly affect the survival and prognosis of patients with lung adenocarcinoma.
Cardioprotection Attributed to Aerobic Exercise-Mediated Inhibition of ALCAT1 and Oxidative Stress-Induced Apoptosis in MI Rats
Authors: Liu Niu , Zhu Yingni , Song Wei , Ren Wujing , Tian Zhenjun
Published: September 2022

Cardiolipin (CL) plays a pivotal role in mitochondria-mediated apoptosis. Acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1) can accelerate CL reactive oxygen production and cause mitochondrial damage. Although we have demonstrated that aerobic exercise significantly reduced ALCAT1 levels in MI mice, what is the temporal characteristic of ALCAT1 after MI? Little is known. Based on this, the effect of exercise on ALCAT1 in MI rats needs to be further verified. Therefore, this paper aimed to characterize ALCAT1 expression, and investigate the possible impact of exercise on ALCAT1 and its role in fibrosis, antioxidant capacity, and apoptosis in MI rats. Our results indicated that the potential utility of MI increased ALCAT1 expression within 1–6 h of MI, and serum CK and CKMB had significant effects in MI at 24 h, while LDH exerted an effect five days after MI. Furthermore, ALCAT1 expression was upregulated, oxidative capacity and excessive apoptosis were enhanced, and cardiac function was decreased after MI, and aerobic exercise can reverse these changes. These findings revealed a previously unknown endogenous cardiac injury factor, ALCAT1, and demonstrated that ALCAT1 damaged the heart of MI rats, and aerobic exercise reduced ALCAT1 expression, oxidative stress, and apoptosis after MI-induced cardiac injury in rats.
Zebrafish: A Useful Animal Model for the Characterization of Drug-Loaded Polymeric NPs
Authors: Bozzer Sara , De Maso Luca , Grimaldi Maria Cristina , Capolla Sara , Dal Bo Michele , Toffoli Giuseppe , Macor Paolo
Published: September 2022

The use of zebrafish (ZF) embryos as an in vivo model is increasingly attractive thanks to different features that include easy handling, transparency, and the absence of adaptive immunity until 4–6 weeks. These factors allow the development of xenografts that can be easily analyzed through fluorescence techniques. In this work, ZF were exploited to characterize the efficiency of drug-loaded polymeric NPs as a therapeutical approach for B-cell malignancies. Fluorescent probes, fluorescent transgenic lines of ZF, or their combination allowed to deeply examine biodistribution, elimination, and therapeutic efficacy. In particular, the fluorescent signal of nanoparticles (NPs) was exploited to investigate the in vivo distribution, while the colocalization between the fluorescence in macrophages and NPs allows following the elimination pathway of these polymeric NPs. Xenotransplanted human B-cells (Nalm-6) developed a reproducible model useful for demonstrating drug delivery by polymeric NPs loaded with doxorubicin and, as a consequence, the arrest of tumor growth and the reduction in tumor burden. ZF proved to be a versatile model, able to rapidly provide answers in the development of animal models and in the characterization of the activity and the efficacy of drug delivery systems.
Irisin Is Related to Non-Alcoholic Fatty Liver Disease (NAFLD)
Authors: Kosmalski Marcin , Drzewoski Józef , Szymczak-Pajor Izabela , Zieleniak Andrzej , Mikołajczyk-Solińska Melania , Kasznicki Jacek , Śliwińska Agnieszka
Published: September 2022

Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, including 46 patients with type 2 diabetes (T2DM]) and the group without NAFLD (n = 66, 31 patients with T2DM). NAFLD was diagnosed based on ultrasound examination, Hepatic Steatosis Index (HSI) and Fatty Liver Index. Baseline anthropometric, blood pressure and biochemical parameters were collected. The serum irisin level was determined using an ELISA test. We observed that NAFLD was associated with an increased concentration of irisin. Moreover, Spearman correlations and linear regression analysis revealed that irisin level correlates with some anthropometric and biochemical parameters such as body mass index, glycated hemoglobin, aspartic aminotransferase, creatinine and urea. Logistic regression analysis depicted that odds for NAFLD increase 1.17 times for each 1 μg/mL rise of irisin concentration. Finally, ROC analysis showed that the concentration of irisin possesses a discriminate capacity for NAFLD and optimal cut points concentration could be designed. The risk of NAFLD in the subgroup with irisin concentration above 3.235 μg/mL was 4.57 times higher than in patients with the lower concentration of irisin. To conclude, the obtained results suggest that irisin concentration is associated with some anthropometric and biochemical parameters and should be further investigated toward its usage as a diagnostic biomarker of NAFLD.
The Pathological Mechanisms of Hearing Loss Caused by KCNQ1 and KCNQ4 Variants
Authors: Homma Kazuaki
Published: September 2022

Deafness-associated genes KCNQ1 (also associated with heart diseases) and KCNQ4 (only associated with hearing loss) encode the homotetrameric voltage-gated potassium ion channels Kv7.1 and Kv7.4, respectively. To date, over 700 KCNQ1 and over 70 KCNQ4 variants have been identified in patients. The vast majority of these variants are inherited dominantly, and their pathogenicity is often explained by dominant-negative inhibition or haploinsufficiency. Our recent study unexpectedly identified cell-death-inducing cytotoxicity in several Kv7.1 and Kv7.4 variants. Elucidation of this cytotoxicity mechanism and identification of its modifiers (drugs) have great potential for aiding the development of a novel pharmacological strategy against many pathogenic KCNQ variants. The purpose of this review is to disseminate this emerging pathological role of Kv7 variants and to underscore the importance of experimentally characterizing disease-associated variants.
Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage
Authors: Wegener Daniel , Aebersold Daniel M. , Grimm Marc-Oliver , Hammerer Peter , Froehner Michael , Graefen Markus , Boehmer Dirk , Zips Daniel , Wiegel Thomas
Published: September 2022

Results of three randomized clinical trials (RCTs) comparing adjuvant radiotherapy (ART) and early salvage radiotherapy (eSRT) of prostate carcinoma and a subsequent meta-analysis of the individual patient data from these RCTs were recently published. The results suggest that early eSRT is as effective and potentially less toxic than ART. Therefore, eSRT should be considered the standard of care. However, due to limitations in the RCTs, ART remains a valid treatment option in patients with the combination of high-risk features such as Gleason Score (GS) 8–10, positive surgical margins (R1) and pathological T-stage 3 or 4 (pT3/4). This article provides a critical appraisal of the RCTs and the rationale for recommendations adopted in the current national guidelines regarding patients with high-risk features after radical prostatectomy (RP): ART should be offered in case of pT3/pT4 and R1 and Gleason Score 8–10; ART can be offered in case of pT3/pT4 and R0 and Gleason Score 8–10 as well as in case of multifocal R1 (including pT2) and Gleason Score 8–10. In any case, the alternative treatment option of eSRT in case of rising PSA should be discussed with the patient.
Explainable AI: A Neurally-Inspired Decision Stack Framework
Authors: Khan Muhammad Salar , Nayebpour Mehdi , Li Meng-Hao , El-Amine Hadi , Koizumi Naoru , Olds James L.
Published: September 2022

European law now requires AI to be explainable in the context of adverse decisions affecting the European Union (EU) citizens. At the same time, we expect increasing instances of AI failure as it operates on imperfect data. This paper puts forward a neurally inspired theoretical framework called “decision stacks” that can provide a way forward in research to develop Explainable Artificial Intelligence (X-AI). By leveraging findings from the finest memory systems in biological brains, the decision stack framework operationalizes the definition of explainability. It then proposes a test that can potentially reveal how a given AI decision was made.
Non-Invasive Microwave-Based Imaging System for Early Detection of Breast Tumours
Authors: Blanco-Angulo Carolina , Martínez-Lozano Andrea , Gutiérrez-Mazón Roberto , Juan Carlos G. , García-Martínez Héctor , Arias-Rodríguez Julia , Sabater-Navarro José M. , Ávila-Navarro Ernesto
Published: September 2022

This work introduces a microwave-based system able to detect tumours in breast phantoms in a non-invasive way. The data acquisition system is composed of a hardware system which involves high-frequency components (antennas, switches and cables), a microcontroller, a vector network analyser used as measurement instrument and a computer devoted to the control and automation of the operation of the system. Concerning the software system, the computer runs a Python script which is in charge of mastering and automatising all the required stages for the data acquisition, from initialisation of the hardware system to performing and saving the measurements. We also report on the design of the high-performance broadband antenna used to carry out the measurements, as well as on the algorithm employed to build the final medical images, based on an adapted version of the so-called Improved Delay-and-Sum (IDAS) algorithm improved by a Hamming window filter and averaging preprocessing. The calibration and start-up of the system are also described. The experimental validation includes the use of different tumour models with different dielectric properties inside the breast phantom. The results show promising tumour detection capabilities, even when there is low dielectric contrast between the tumoural and healthy tissues, as is the usual case for dense breasts in young women.