bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Trace Element Status in Camels: A Review
Authors: Abdelrahman Mutassim M. , Alhidary Ibrahim A. , Aljumaah Riyadh S. , Faye Bernard
Published: August 2022

Trace minerals play an important role in animal health and productivity. They are involved also in many physiological activities, and their deficiency causes a variety of pathological problems and metabolic defects, reducing consequently the animal productivity. The demand for animal products in semi-arid areas is rapidly increasing, and the supply is still below the required level, partially due to low animal productivity. Camels (Camelus dromedarius and Camelus bactrianus) are considered one of the main sources of healthy, high-quality meat and milk for human consumption within most of the countries in the semi-arid regions. Despite their efficient adaptation to their environment, camels can suffer from the growth retardation of newborns, low feed efficiency, anemia, poor fertility, poor reproduction and many other metabolic disorders. It is well known that trace mineral deficiencies and trace mineral toxicities can influence camels’ production and reproductive efficiency, as well as many aspects of their growth and metabolism. Evaluating the trace minerals status of camels and their variability is an obvious step toward improving camels’ productivity and health. Thus, the present article reviews the data regarding the status of trace minerals (copper, zinc, iron, selenium, manganese, cobalt, iodine, fluorine, molybdenum, sulfur, bromide and nickel) in camel blood and their physiological variability, with a focus on their deficiency and toxicity effects.
Microbial Profiling of Potato-Associated Rhizosphere Bacteria under Bacteriophage Therapy
Authors: Mousa Samar , Magdy Mahmoud , Xiong Dongyan , Nyaruabaa Raphael , Rizk Samah Mohamed , Yu Junping , Wei Hongping
Published: August 2022

Potato soft rot and wilt are economically problematic diseases due to the lack of effective bactericides. Bacteriophages have been studied as a novel and environment-friendly alternative to control plant diseases. However, few experiments have been conducted to study the changes in plants and soil microbiomes after bacteriophage therapy. In this study, rhizosphere microbiomes were examined after potatoes were separately infected with three bacteria (Ralstonia solanacearum, Pectobacterium carotovorum, Pectobacterium atrosepticum) and subsequently treated with a single phage or a phage cocktail consisting of three phages each. Results showed that using the phage cocktails had better efficacy in reducing the disease incidence and disease symptoms’ levels when compared to the application of a single phage under greenhouse conditions. At the same time, the rhizosphere microbiota in the soil was affected by the changes in micro-organisms’ richness and counts. In conclusion, the explicit phage mixers have the potential to control plant pathogenic bacteria and cause changes in the rhizosphere bacteria, but not affect the beneficial rhizosphere microbes.
Characteristics of Antibiotic Resistance and Tolerance of Environmentally Endemic Pseudomonas aeruginosa
Authors: Kim Seryoung , Masai Satomi , Murakami Keiji , Azuma Momoyo , Kataoka Keiko , Sebe Mayu , Shimizu Kazuya , Itayama Tomoaki , Whangchai Niwooti , Whangchai Kanda , Ihara Ikko , Maseda Hideaki
Published: August 2022

Antibiotic-resistant bacteria remain a serious public health threat. In order to determine the percentage of antibiotic-resistant and -tolerant Pseudomonas aeruginosa cells present and to provide a more detailed infection risk of bacteria present in the environment, an isolation method using a combination of 41 °C culture and specific primers was established to evaluate P. aeruginosa in the environment. The 50 strains were randomly selected among 110 isolated from the river. The results of antibiotic susceptibility evaluation showed that only 4% of environmental strains were classified as antibiotic-resistant, while 35.7% of clinical strains isolated in the same area were antibiotic-resistant, indicating a clear difference between environmental and clinical strains. However, the percentage of antibiotic-tolerance, an indicator of potential resistance risk for strains that have not become resistant, was 78.8% for clinical strains and 90% for environmental strains, suggesting that P. aeruginosa, a known cause of nosocomial infections, has a high rate of antibiotic-tolerance even in environmentally derived strains. It suggested that the rate of antibiotic-tolerance is not elicited by the presence or absence of antimicrobial exposure. The combination of established isolation and risk analysis methods presented in this study should provide accurate and efficient information on the risk level of P. aeruginosa in various regions and samples.
Celastrol: A Promising Agent Fighting against Cardiovascular Diseases
Authors: Li Zhexi , Zhang Jingyi , Duan Xulei , Zhao Guoan , Zhang Min
Published: August 2022

Cardiovascular diseases (CVD) are leading causes of morbidity and mortality worldwide; therefore, seeking effective therapeutics to reduce the global burden of CVD has become increasingly urgent. Celastrol, a bioactive compound isolated from the roots of the plant Tripterygium wilfordii (TW), has been attracting increasing research attention in recent years, as it exerts cardiovascular treatment benefits targeting both CVD and their associated risk factors. Substantial evidence has revealed a protective role of celastrol against a broad spectrum of CVD including obesity, diabetes, atherosclerosis, cerebrovascular injury, calcific aortic valve disease and heart failure through complicated and interlinked mechanisms such as direct protection against cardiomyocyte hypertrophy and death, and indirect action on oxidation and inflammation. This review will mainly summarize the beneficial effects of celastrol against CVD, largely based on in vitro and in vivo preclinical studies, and the potential underlying mechanisms. We will also briefly discuss celastrol’s pharmacokinetic limitations, which hamper its further clinical applications, and prospective future directions.
Gq Signaling in Autophagy Control: Between Chemical and Mechanical Cues
Authors: Navarro-Lérida Inmaculada , Aragay Anna M. , Asensio Alejandro , Ribas Catalina
Published: August 2022

All processes in human physiology relies on homeostatic mechanisms which require the activation of specific control circuits to adapt the changes imposed by external stimuli. One of the critical modulators of homeostatic balance is autophagy, a catabolic process that is responsible of the destruction of long-lived proteins and organelles through a lysosome degradative pathway. Identification of the mechanism underlying autophagic flux is considered of great importance as both protective and detrimental functions are linked with deregulated autophagy. At the mechanistic and regulatory levels, autophagy is activated in response to diverse stress conditions (food deprivation, hyperthermia and hypoxia), even a novel perspective highlight the potential role of physical forces in autophagy modulation. To understand the crosstalk between all these controlling mechanisms could give us new clues about the specific contribution of autophagy in a wide range of diseases including vascular disorders, inflammation and cancer. Of note, any homeostatic control critically depends in at least two additional and poorly studied interdependent components: a receptor and its downstream effectors. Addressing the selective receptors involved in autophagy regulation is an open question and represents a new area of research in this field. G-protein coupled receptors (GPCRs) represent one of the largest and druggable targets membrane receptor protein superfamily. By exerting their action through G proteins, GPCRs play fundamental roles in the control of cellular homeostasis. Novel studies have shown Gαq, a subunit of heterotrimeric G proteins, as a core modulator of mTORC1 and autophagy, suggesting a fundamental contribution of Gαq-coupled GPCRs mechanisms in the control of this homeostatic feedback loop. To address how GPCR-G proteins machinery integrates the response to different stresses including oxidative conditions and mechanical stimuli, could provide deeper insight into new signaling pathways and open potential and novel therapeutic strategies in the modulation of different pathological conditions.
MARCKS Is an Essential Regulator of Reactive Oxygen Species Production in the Monocytic Cell Type
Authors: Huber René , Diekmann Mareike , Hoffmeister Leonie , Kühl Friederike , Welz Bastian , Brand Korbinian
Published: August 2022

Myristoylated alanine-rich C-kinase substrate (MARCKS) is a ubiquitous protein mediating versatile effects in a variety of cell types, including actin crosslinking, signal transduction, and intracellular transport processes. MARCKS’s functional role in monocyte/macrophages, however, has not yet been adequately addressed. Thus, the aim of this study was to further elucidate the impact of MARCKS on central cellular functions of monocytic cells. To address this topic, we generated monocytic THP-1 (Tohoku Hospital Pediatrics-1)-derived MARCKS wildtype and knockout (KO) cells using the CRISPR/Cas9 technique. Remarkably, in the absence of MARCKS, both total and intracellular reactive oxygen species (ROS) production were strongly suppressed but restored following transient MARCKS re-transfection. In contrast, proliferation, differentiation, cytokine expression, and phagocytosis remained unaltered. A complete inhibition of ROS production could also be achieved in THP-1-derived PKCβ KO cells or in PKC inhibitor Staurosporine-treated primary human monocytes. MARCKS deficiency also involved reduced basal Akt phosphorylation and delayed re-phosphorylation. Further analyses indicated that long-term TNF pre-incubation strongly enhances monocytic ROS production, which was completely blocked in MARCKS and PKCβ KO cells. Collectively, our study demonstrates that MARCKS is an essential molecule enabling ROS production by monocytic cells and suggests that MARCKS is part of a signal cascade involved in ROS formation.
Effect of Mechanical Activation on the Leaching Process of Rare Earth Metal Yttrium in Deep Eutectic Solvents
Authors: Li Xiaofen , Li Wei , Gao Yuntao , Tian Guocai
Published: August 2022

Deep eutectic solvents (DESs) have the potential to be a lixiviant for the selective processing of metal because of their versatile complexation properties. In this study, the leaching behavior of rare-earth carbonate before and after mechanical activation in chloride–urea–malonic acid, the deep eutectic solvents (ChCl-urea-MA DESs) were investigated. Leaching experiments were employed to investigate the effects of reaction temperature and activation time on the leaching efficiency of the metal, yttrium, in DESs. The leaching efficiency of yttrium was determined to be 85.2% when the activation time was 60 min, the leaching temperature was 80 °C and the leaching time was 12 h. The findings showed that mechanical activation increased the yttrium leaching efficiency from 48.61 to 88.37% by lowering the particle size and increasing the contact area of the reaction. The investigation of the yttrium leaching kinetics revealed that, after mechanical grinding, the apparent activation energy of rare-earth carbonate decreased from 83.88 kJ∙mol−1 to 37.4 kJ∙mol−1, and the leaching process of the sample changed from controlled by chemical reaction to controlled by diffusion in the solid product layer. Mechanical activation combined with DESs was proposed as an eco-friendly, sustainable, and effective alternative to conventional mineral acid leaching and solvent, with advantages such as moderate conditions, reusability of the DESs, and no additional wastewater produced. The findings of the study show this method is a good way to recycle rare-earth metals.
A Proactive Approach to Extended Vehicle Routing Problem with Drones (EVRPD)
Authors: Sitek Paweł , Wikarek Jarosław , Jagodziński Mieczysław
Published: August 2022

Unmanned aerial vehicles (UAVs), also known as drones, are increasingly common and popular due to their relatively low prices and high mobility. The number of areas for their practical applications is rapidly growing. The most promising are: last-mile delivery, emergency response, the inspection of technical devices and installations, etc. In these applications, it is often necessary to solve vehicle routing problems, formulated as a variant of the vehicle routing problems with drones (VRPD). This study presents a proactive approach to a modified and extended VRPD, including: the dynamic selection of drone take-off points, bidirectional delivery (delivery and pick up), various types of shipments, allocation of shipments to drones and drones to vehicles, the selection of the optimal number of drones, etc. Moreover, a formal model of constraints and questions for the extended vehicle routing problem with drones (EVRPD) and exact and approximate methods for solving it have been proposed. The proposed model can be the basis for supporting proactive and reactive decisions regarding last-mile delivery, particularly the selection of the necessary fleet, starting points, the identification of specific shipments that prevent delivery with available resources, etc. The study also includes the results of numerous computational experiments verifying the effectiveness of the implementation methods. The time to obtain a solution is at least 20 times shorter for the proposed DGA (dedicated genetic algorithm) than for the mathematical programming solvers such as Gurobi or LINGO. Moreover, for larger-sized data instances, these solvers do not allow obtaining any solution in an acceptable time, or they obtain worse solutions.
Antibacterial Activity and Kinetic Release of Laureliopsis philippiana (Looser) Essential Oil from Nanostructured Porous Silicon with Surface-Functionalization Alternatives
Authors: Pérez-San Martín Andrés , Uribe Karina , Hernández-Montelongo Jacobo , Naveas Nelson , Manso-Silván Miguel , Oyarzún Patricio , Díaz-García Víctor , Contreras Braulio , Recio-Sánchez Gonzalo
Published: August 2022

In this work, the antibacterial activity of Laureliopsis philippiana (Looser) essential oil was studied, and its kinetic release performance using different surface-functionalized nanostructured porous silicon (nPSi) was analyzed. Experimental results showed the high inhibitory effect of Laureliopsis philippiana essential oil against Staphylococcus aureus and Klebsiella pneumoniae. In addition, the essential oil was successfully loaded into different kinds of functionalized nPSi. FTIR measurements indicated the formation of stable complexes in the nPSi functionalization process. Specifically, chemical oxidized nPSi (nPSi-Ox), 3-aminopropyltriethoxysilane functionalized nPSi (nPSi-APTS), undecylenic acid-functionalized nPSi (nPSi-UAc), chitosan (nPSi-Chi) and β-cyclodextrin (nPSi-βCD) polymer functionalization on nPSi were studied. nPSi-Ox, nPSi-APTS, and nPSi-UAc were covalent functionalization, and nPSi-Chi and nPSi-βCD were obtained by electrostatic attachment. The kinetic study demonstrated a controlled release of up to 4 h for all the samples following a quasi-Fickian diffusion mechanism. Moreover, the use of functionalized nPSi-APTS and nPSi-UAc structures allows a more controlled kinetic release of Laureliopsis philippiana essential oil in comparison to the rest of the functionalization, increasing its availability and exposure to the environment.
2D/3D Multimode Medical Image Alignment Based on Spatial Histograms
Authors: Ban Yuxi , Wang Yang , Liu Shan , Yang Bo , Liu Mingzhe , Yin Lirong , Zheng Wenfeng
Published: August 2022

The key to image-guided surgery (IGS) technology is to find the transformation relationship between preoperative 3D images and intraoperative 2D images, namely, 2D/3D image registration. A feature-based 2D/3D medical image registration algorithm is investigated in this study. We use a two-dimensional weighted spatial histogram of gradient directions to extract statistical features, overcome the algorithm’s limitations, and expand the applicable scenarios under the premise of ensuring accuracy. The proposed algorithm was tested on CT and synthetic X-ray images, and compared with existing algorithms. The results show that the proposed algorithm can improve accuracy and efficiency, and reduce the initial value’s sensitivity.
Aqueous Synthesis of the Tiopronin-Capped Gold Nanoclusters/Nanoparticles with Precise Size Control via Deprotonation of the Ligand
Authors: Kang Daekyung , Son Changhee , Lee Hakseon , Park Hongsik , Kim Taewan , Park Jonghoo
Published: August 2022

Gold nanoparticles have led to numerous advances in nanomaterial-based sensors and biomedical technologies owing to their chemical inertness and outstanding physiochemical and optical properties. Gold nanoparticles are still considered one of the most promising types of nanomaterials in various biomedical fields, including drug delivery, cancer therapy, biomolecule detection, and high-accuracy diagnosis. Surface functionalization of gold nanoparticles with various ligands modifies the physicochemical properties of the surface, thereby improving the biocompatibility and uptake efficiency of a living system. Tiopronin, one of the most commonly used ligands for gold nanoparticles, has both thiol and carboxyl functional groups that can be easily attached to various biomolecules. However, the conventional method of synthesizing tiopronin-capped gold nanoclusters using methanol and acetic acid as a solvent requires a laborious and time-consuming dialysis process to remove methanol and acetic acid. In this study, we demonstrate a novel and simple aqueous synthesis method to obtain tiopronin-capped gold nanoclusters/nanoparticles with precise size control in the sub-nanometer to nanometer range. The main advantage of our synthesis method is that it does not require a dialysis process because it uses water as a solvent. The boron byproduct produced during the synthesis can be removed with a simple volatilization process. Moreover, we characterized the physical morphologies, photoelectronic properties, hydrodynamic size, and crystal structure of the tiopronin-capped gold nanoclusters/nanoparticles using transmission electron microscopy, spectrophotometry, fluorescence spectrometry, dynamic light scattering, zeta potential, and X-ray diffraction.
LCHP Diet Enriched with Cholesterol Promotes Non-Alcoholic Fatty Liver Disease in Wistar Rats
Authors: Kostogrys Renata B. , Franczyk-Żarów Magdalena , Kus Edyta , Topolska Kinga
Published: August 2022

The aim of this study was to analyze the effect of a low-carbohydrate–high-protein diet, enriched with cholesterol (LCHPch), on body weight, lipid metabolism, as well as kidney and liver function in rats. Wistar rats (N = 18, male) were randomly allocated into experimental groups and fed a modified AIN-93G diet with the addition of 1% cholesterol (AINch, WDch and LCHPch diets) for 8 weeks. Despite the lack of significant differences in the final body weight and liver weight of animals, the kidneys of rats in the LCHPch group were considerably heavier compared to the control group. Serum total cholesterol and the sum of low- and very-low-density fractions of cholesterol as well as ALT activity were significantly increased in the LCHPch rats in comparison to the AINch group. Simultaneously, the highest content of liver fat was obtained for animals from LCHPch group. It was also shown that both WDch and LCHPch diets significantly changed fatty acid profile in the adipose tissue of rats compared to control, with a significant increase in SFA and MUFA and a decrease in PUFA. Non-alcoholic fatty liver disease was observed in rats fed not only WDch but also LCHPch diets. The detailed mechanism still needs to be investigated to prevent the organism from the harmful effects of macronutrient dietary imbalance.
Research on Unsupervised Classification Algorithm Based on SSVEP
Authors: Wu Yingnian , Yang Rui , Chen Wenbai , Li Xin , Niu Jiaxin
Published: August 2022

Filter Bank Canonical Correlation Analysis (FBCCA) is used to classify electroencephalography (EEG) signals to overcome insufficient training data for EEG signal classification. This approach is not constrained by the training data or time and also performs unsupervised Steady-State Visual Evoked Potential (SSVEP) classification in a short time, which is easy to extend and optimize. By examining the data set from the Brain–Computer Interface (BCI) contest and comparing it to Canonical Correlation Analysis (CCA) using various parameter settings, the results show that FBCCA carries better classification performance than CCA. When the number of harmonics is 4 and the number of subbands is 5, the identification rate of 40 targets with the frequency difference of 0.2 Hz achieves 88.9%, and the maximum information transfer rate (ITR) achieves 88.64 bits/min, which shows superior compatibility and practicability.
A Global Analysis of Research Outputs on Neurotoxicants from 2011–2020: Adverse Effects on Humans and the Environment
Authors: Tywabi-Ngeva Zikhona , Adeniji Abiodun Olagoke , Okaiyeto Kunle
Published: August 2022

Neurotoxicants are detrimental to the mammalian nervous system at higher concentrations after exposure, and could result in several neurological abnormalities, especially on the nervous and reproductive systems, and sometimes death. The present study, therefore, aimed to evaluate the research growth on neurotoxicants and their effects on humans and the environment over the last decade from 2011 to 2020. Data on this subject were obtained from the SCI-Expanded of Web of Science, and analyses were performed on the retrieved data in RStudio. The number of published documents fluctuated over the studied years, with an annual growth rate of 4.46%, and the highest number of publications were recorded in 2020 (n = 40). Single authored documents, documents per author, authors per documents, and collaboration index were 24, 0.219, 4.57, and 4.87, respectively. Networks of collaboration in this study were noticeable among authors, institutions, and countries; thus, making efforts to strengthen networking globally would be a good idea. Results from this study also show that the growing trend of research in the field is quite encouraging, thus providing future directions to upcoming researchers, and contributes immensely to reducing the exposure and several disorders linked to these neurotoxicants globally.
Chatter Detection in Robotic Milling Using Entropy Features
Authors: Yang Bin , Guo Kai , Sun Jie
Published: August 2022

Chatter detection in robotic milling is a difficult issue due to the complex dynamic behavior of robots. In this paper, a novel approach to detecting chatter in the robotic milling process is proposed. The method of improved complete ensemble empirical mode decomposition with adaptive noise is introduced for decomposing the milling vibration signals into a series of intrinsic mode functions (IMFs). The effective IMFs are chosen according to the correlation between the original signals and each IMF. Signal reconstruction is conducted using the selected IMFs. The weighted refined composite multiscale dispersion entropy is extracted from the reconstructed signals in order to characterize the chatter states. Then, a classification model is established for chatter detection. Experimental results prove that the proposed method is feasible for chatter detection in the robotic milling process under different robot configurations and machining parameters.
Research on the Influence of Weather Patterns on Ozone Concentration: A Case Study in Tianjin
Authors: Li Yuan , Wang Jiguang , Li Liwei , Bai Yu , Gao Jingyun , He Lei , Tang Miao , Yang Ning
Published: August 2022

Ozone (O3) is an important secondary substance that plays a significant role in atmospheric chemistry and climate change. Although O3 is essential in the stratosphere, it is harmful to human health in the troposphere, where this study was conducted. In recent years, O3 pollution in the Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD) regions has deteriorated, which has become an important environmental problem. The generation of O3 is closely related to meteorological factors. In this study, the weather classification method was adopted to study the effect of meteorological conditions on O3 concentration. In the BTH region, Tianjin was selected as the representative city for the research. The real-time pollutants data, meteorological re-analysis data, and meteorological data in 2019 were combined for the analysis. The subjective weather classification method was adopted to investigate the effects of different weather types on O3 concentration. The backward trajectory tracking model was used to explore the characteristics and changes of O3 pollution under two extreme weather types. The results indicate there is a good correlation between O3 concentration and ambient temperature. Under the control of low pressure on the ground and the influence of southwest airflow in the upper air for Tianjin, heavy O3 pollution occurred frequently. The addition of external transport and local generation will cause high O3 values when the weather system is weak. The O3 concentration is closely related to ambient temperature. Continuous high-temperature weather is conducive to the photochemical reaction. The multi-day O3 pollution process would occur when the weather system is robust. The first and second types of extreme weather are more likely to cause persistent O3 pollution processes. Under the premise of stable emission sources, the change in weather patterns was the main reason affecting the O3 concentration. This study aims to improve O3 pollution control and air quality prediction in the BTH region and large cities in China.
Revealing the Effects of Water Imbibition on Gas Production in a Coalbed Matrix Using Affected Pore Pressure and Permeability
Authors: Lou Yi , Su Yuliang , Wang Ke , Xia Peng , Wang Wendong , Xiong Wei , Shao Linjie , Yang Fuqin
Published: August 2022

The effect of water imbibition on characteristics of coalbed methane reservoirs, such as permeability, gas occurrence state, and gas production, is controversial. According to the mechanism of imbibition, gas and water distribution in blind pores is reconfigured during the fracturing process. Therefore, a new comprehensive model of pore pressure and permeability, based on the perfect gas equation and the weighted superposition of viscous flow and Knudsen diffusion, was established for micro- and nanoscale blind pores during water drainage. Using the numerical simulation module in the Harmony software, the effects of imbibition on coal pore pressure, permeability, and gas production were analyzed. The results showed that (1) water imbibition can increase pore pressure and reduce permeability, and (2) water imbibition is not always deleterious to gas production and estimated ultimate reserve (EUR), when the imbibition is constant, the thicker water film is deleterious to coalbed methane wells; when the thickness of water film is constant, more imbibition is beneficial to gas production and EUR. This research is beneficial to optimize the operation of well shut-ins after fracturing and provides methods for optimizing key parameters of gas reservoirs and insights into understanding the production mechanism of coalbed methane wells.
Bitcoin as a Safe-Haven Asset and a Medium of Exchange
Authors: Yan Yu , Lei Yiming , Wang Yiming
Published: August 2022

A monetary model is established to introduce that bitcoin does have the characteristics of a price rise when the economic situation is terrible under high risk aversion. At this time, Bitcoin has the property of a safe-haven asset, and when economic conditions are good and risk aversion is low, Bitcoin has a pro-cyclical nature. At this time, Bitcoin has a stronger property as a medium of exchange. To show the movement law of the bitcoin price, we make a logarithmic linearization of the model and simulation, and the result is consistent with the theoretical analysis. To better understand the role of bitcoin in the real economy, several standard portfolio models are used to measure the similarities and differences between gold and bitcoin in an investment portfolio. After the outbreak of COVID-19, bitcoin has shown stronger safe-haven asset properties.
A Holistic Scalability Strategy for Time Series Databases Following Cascading Polyglot Persistence
Authors: Calatrava Carlos Garcia , Fontal Yolanda Becerra , Cucchietti Fernando M.
Published: August 2022

Time series databases aim to handle big amounts of data in a fast way, both when introducing new data to the system, and when retrieving it later on. However, depending on the scenario in which these databases participate, reducing the number of requested resources becomes a further requirement. Following this goal, NagareDB and its Cascading Polyglot Persistence approach were born. They were not just intended to provide a fast time series solution, but also to find a great cost-efficiency balance. However, although they provided outstanding results, they lacked a natural way of scaling out in a cluster fashion. Consequently, monolithic approaches could extract the maximum value from the solution but distributed ones had to rely on general scalability approaches. In this research, we proposed a holistic approach specially tailored for databases following Cascading Polyglot Persistence to further maximize its inherent resource-saving goals. The proposed approach reduced the cluster size by 33%, in a setup with just three ingestion nodes and up to 50% in a setup with 10 ingestion nodes. Moreover, the evaluation shows that our scaling method is able to provide efficient cluster growth, offering scalability speedups greater than 85% in comparison to a theoretically 100% perfect scaling, while also ensuring data safety via data replication.
Hypoxia Affects HIF-1/LDH-A Signaling Pathway by Methylation Modification and Transcriptional Regulation in Japanese Flounder (Paralichthys olivaceus)
Authors: Liu Binghua , Wen Haishen , Yang Jun , Li Xiaohui , Li Guangling , Zhang Jingru , Wu Shuxian , Butts Ian AE , He Feng
Published: August 2022

Japanese flounder (Paralichthys olivaceus) responsive mechanisms to hypoxia are still not fully understood. Therefore, we performed an acute hypoxic treatment (dissolved oxygen at 2.07 ± 0.08 mg/L) on Japanese flounder. It was confirmed that the hypoxic stress affected the physiological phenotype through changes in blood physiology (RBC, HGB, WBC), biochemistry (LDH, ALP, ALT, GLU, TC, TG, ALB), and hormone (cortisol) indicators. Hypoxia inducible factor-1 (HIF-1), an essential oxygen homeostasis mediator in organisms consisting of an inducible HIF-1α and a constitutive HIF-1β, and its target gene LDH-A were deeply studied. Results showed that HIF-1α and LDH-A genes were co-expressed and significantly affected by hypoxic stress. The dual-luciferase reporter assay confirmed that transcription factor HIF-1 transcriptionally regulated the LDH-A gene, and its transcription binding sequence was GGACGTGA located at −2343~−2336. The DNA methylation status of HIF-1α and LDH-A genes were detected to understand the mechanism of environmental stress on genes. It was found that hypoxia affected the HIF-1α gene and LDH-A gene methylation levels. The study uncovered HIF-1/LDH-A signaling pathway responsive mechanisms of Japanese flounder to hypoxia in epigenetic modification and transcriptional regulation. Our study is significant to further the understanding of environmental responsive mechanisms as well as providing a reference for aquaculture.
A Review of Biomarkers of Cardiac Allograft Rejection: Toward an Integrated Diagnosis of Rejection
Authors: Coutance Guillaume , Desiré Eva , Duong Van Huyen Jean-Paul
Published: August 2022

Despite major advances in immunosuppression, allograft rejection remains an important complication after heart transplantation, and it is associated with increased morbidity and mortality. The gold standard invasive strategy to monitor and diagnose cardiac allograft rejection, based on the pathologic evaluation of endomyocardial biopsies, suffers from many limitations including the low prevalence of rejection, sample bias, high inter-observer variability, and international working formulations based on arbitrary cut-offs that simplify the landscape of rejection. The development of innovative diagnostic and prognostic strategies—integrating conventional histology, molecular profiling of allograft biopsy, and the discovery of new tissue or circulating biomarkers—is one of the major challenges of translational medicine in solid organ transplantation, and particularly in heart transplantation. Major advances in the field of biomarkers of rejection have paved the way for a paradigm shift in the monitoring and diagnosis of cardiac allograft rejection. We review the recent developments in the field, including non-invasive biomarkers to minimize the number of protocol endomyocardial biopsies and tissue biomarkers as companion tools of pathology to refine the diagnosis of cardiac rejection. Finally, we discuss the potential role of these biomarkers to provide an integrated bio-histomolecular diagnosis of cardiac allograft rejection.
Development of Artificial System to Induce Chromatin Loosening in Saccharomyces cerevisiae
Authors: Yamamoto Ryota , Sato Genki , Amai Takamitsu , Ueda Mitsuyoshi , Kuroda Kouichi
Published: August 2022

In eukaryotic cells, loosening of chromatin causes changes in transcription and DNA replication. The artificial conversion of tightly packed chromatin (heterochromatin) to loosely packed chromatin (euchromatin) enables gene expression and regulates cell differentiation. Although some chemicals convert chromatin structures through histone modifications, they lack sequence specificity. This study attempted to establish a novel technology for inducing chromatin loosening in target regions of Saccharomyces cerevisiae. We focused on histone acetylation, which is one of the mechanisms of euchromatin induction. The sequence-recognizing ability of the dead Cas9 (dCas9) and guide RNA (gRNA) complex was used to promote histone acetylation at a targeted genomic locus. We constructed a plasmid to produce a fusion protein consisting of dCas9 and histone acetyltransferase Gcn5 and a plasmid to express gRNA recognizing the upstream region of heterochromatic URA3. Confocal microscopy revealed that the fusion proteins were localized in the nucleus. The yeast strain producing the fusion protein and gRNA grew well in the uracil-deficient medium, while the strain harboring empty plasmids or the strain containing the mutations that cause loss of nucleosomal histone acetylation activity of Gcn5 did not. This suggests that the heterochromatin was loosened as much as euchromatin through nucleosomal histone acetylation. The amount of euchromatic DNA at the target locus increased, indicating that chromatin loosening was induced by our system. Nucleosomal histone acetylation in heterochromatic loci by our developed system is a promising method for inducing euchromatic state in a target locus.
Do Apixaban Plasma Levels Relate to Bleeding? The Clinical Outcomes and Predictive Factors for Bleeding in Patients with Non-Valvular Atrial Fibrillation
Authors: Limcharoen Sutee , Pongchaidecha Manat , Pimsi Piyarat , Limprasert Sarawuth , Suphanklang Juthathip , Saelim Weerayuth , Santimaleeworagun Wichai , Boonmuang Pornwalai
Published: August 2022

Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5–95th percentiles: 68.69–207.8) μg/L and 185.62 (5–95th percentiles: 124.06–384.34) μg/L for the apixaban trough (Ctrough) and apixaban peak plasma levels (Cpeak), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for Ctrough and Cpeak in the stroke and non-stroke groups, respectively. The median of Ctrough (139.15 μg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 μg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54–176.64; and p-value = 0.002) and Ctrough (OR: 1.01; 95%: CI 1.00–1.03; and p-value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.
Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases
Authors: Souza Olívia Fonseca , Popi Ana Flavia
Published: August 2022

B-cell development is a very orchestrated pathway that involves several molecules, such as transcription factors, cytokines, microRNAs, and also different cells. All these components maintain the ideal microenvironment and control B-cell differentiation. MicroRNAs are small non-coding RNAs that bind to target mRNA to control gene expression. These molecules could circulate in the body in a free form, protein-bounded, or encapsulated into extracellular vesicles, such as exosomes. The comprehension of the role of microRNAs in the B-cell development was possible based on microRNA profile of each B-cell stage and functional studies. Herein, we report the knowledge about microRNAs in the B-cell the differentiation, proliferation, and also in hematological malignancies.
Subsequent Systemic Therapy following Platinum and Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma
Authors: Hong Joohyun , Sung Hyun Hwan , Jeong Byong Chang , Park Se Hoon
Published: August 2022

Treatment of metastatic urothelial carcinoma (mUC) after failure with platinum-based chemotherapy and immune checkpoint inhibitors (ICIs) remains controversial. To explore the role of subsequent systemic therapy, medical records from 436 patients who were consecutively treated with chemotherapy for mUC between May 2017 and April 2021 were collected from a single-center cancer registry. The primary endpoint was overall survival (OS), and progression-free survival (PFS) and response rate (RR) were also assessed. Among the 318 patients who failed both platinum and ICIs, subsequent therapy was delivered to 166 (52%) patients: taxanes (n = 56), platinum rechallenge (n = 46), pemetrexed (n = 39), and clinical trials (n = 25). Objective responses to third-line therapy were noted in 50 patients (RR, 30%; 95% CI, 23–37%). The patients who were enrolled in clinical trials and treated with platinum rechallenge were significantly more likely to respond than those treated with taxanes or pemetrexed. The median PFS and OS were 3.5 months (95% CI, 2.9–4.2 months) and 9.5 months (95% CI, 8.1–11.0 months), respectively. Similar to RR, PFS and OS were longer for the patients who were enrolled in clinical trials. Based on multivariate analyses, good performance status and enrollment in clinical trials are associated with benefits from subsequent therapy for pretreated mUC.
Functional Connectivity Increases in Response to High-Definition Transcranial Direct Current Stimulation in Patients with Chronic Disorder of Consciousness
Authors: Han Jinying , Chen Chen , Zheng Shuang , Zhou Ting , Hu Shunyin , Yan Xiaoxiang , Wang Changqing , Wang Kai , Hu Yajuan
Published: August 2022

High-definition transcranial direct current stimulation (HD-tDCS) has been shown to play an important role in improving consciousness in patients with disorders of consciousness (DOCs), but its neuroelectrophysiological evidence is still lacking. To better explain the electrophysiological mechanisms of the effects of HD-tDCS on patients with DOCs, 22 DOC patients underwent 10 anodal HD-tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC). This study used the Coma Recovery Scale-Revised (CRS-R) to assess the level of consciousness in DOC patients. According to whether the CRS-R score increased before and after stimulation, DOC patients were divided into a responsive group and a non-responsive group. By comparing the differences in resting-state EEG functional connectivity between different frequency bands and brain regions, as well as the relationship between functional connectivity values and clinical scores, the electrophysiological mechanism of the clinical effects of HD-tDCS was further explored. The change of the phase locking value (PLV) on the theta frequency band in the left frontal–parietooccipital region was positively correlated with the change in the CRS-R scores. As the number of interventions increased, we observed that in the responsive group, the change in PLV showed an upward trend, and the increase in the PLV appeared in the left frontal–parietooccipital region at 4–8 Hz and in the intra-bifrontal region at 8–13 Hz. In the non-responsive group, although the CRS-R scores did not change after stimulation, the PLV showed a downward trend, and the decrease in the PLV appeared in the intra-bifrontal region at 8–13 Hz. In addition, at the three-month follow-up, patients with increased PLV in the intra-bifrontal region at 8–13 Hz after repeated HD-tDCS stimulation had better outcomes than those without. Repeated anodal stimulation of the left DLPFC with HD-tDCS resulted in improved consciousness in some patients with DOCs. The increase in functional connectivity in the brain regions may be associated with the improvement of related awareness after HD-tDCS and may be a predictor of better long-term outcomes.
The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway
Authors: Almasabi Faris , van Zwieten Gusta , Alosaimi Faisal , Smit Jasper V. , Temel Yasin , Janssen Marcus L. F. , Jahanshahi Ali
Published: August 2022

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.
Only Words Count; the Rest Is Mere Chattering: A Cross-Disciplinary Approach to the Verbal Expression of Emotional Experience
Authors: Laricchiuta Daniela , Termine Andrea , Fabrizio Carlo , Passarello Noemi , Greco Francesca , Piras Fabrizio , Picerni Eleonora , Cutuli Debora , Marini Andrea , Mandolesi Laura , Spalletta Gianfranco , Petrosini Laura
Published: August 2022

The analysis of sequences of words and prosody, meter, and rhythm provided in an interview addressing the capacity to identify and describe emotions represents a powerful tool to reveal emotional processing. The ability to express and identify emotions was analyzed by means of the Toronto Structured Interview for Alexithymia (TSIA), and TSIA transcripts were analyzed by Natural Language Processing to shed light on verbal features. The brain correlates of the capacity to translate emotional experience into words were determined through cortical thickness measures. A machine learning methodology proved that individuals with deficits in identifying and describing emotions (n = 7) produced language distortions, frequently used the present tense of auxiliary verbs, and few possessive determiners, as well as scarcely connected the speech, in comparison to individuals without deficits (n = 7). Interestingly, they showed high cortical thickness at left temporal pole and low at isthmus of the right cingulate cortex. Overall, we identified the neuro-linguistic pattern of the expression of emotional experience.
Overcoming Resistance to HER2-Directed Therapies in Breast Cancer
Authors: Schlam Ilana , Tarantino Paolo , Tolaney Sara M.
Published: August 2022

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for around 15% of all breast cancers and was historically associated with a worse prognosis compared with other breast cancer subtypes. With the development of HER2-directed therapies, the outcomes of patients with HER2-positive disease have improved dramatically; however, many patients present with de novo or acquired resistance to these therapies, which leads to early recurrences or progression of advanced disease. In this narrative review, we discuss the mechanisms of resistance to different HER2-targeted therapies, including monoclonal antibodies, small tyrosine kinase inhibitors, and antibody-drug conjugates. We review mechanisms such as impaired binding to HER2, incomplete receptor inhibition, increased signaling from other receptors, cross-talk with estrogen receptors, and PIK3CA pathway activation. We also discuss the role of the tumor immune microenvironment and HER2-heterogeneity, and the unique mechanisms of resistance to novel antibody-drug conjugates. A better understanding of these mechanisms and the potential strategies to overcome them will allow us to continue improving outcomes for patients with breast cancer.
The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC
Authors: Wang Dan , Li Yuqiang , Ge Heming , Ghadban Tarik , Reeh Matthias , Güngör Cenap
Published: August 2022

Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease.