bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum Information Entropy for a Hyperbolic Double Well Potential in the Fractional Schrödinger Equation
Authors: Santana-Carrillo R. , Peto J. M. Velázquez , Sun Guo-Hua , Dong Shi-Hai
Published: June 2023

In this study, we investigate the position and momentum Shannon entropy, denoted as Sx and Sp, respectively, in the context of the fractional Schrödinger equation (FSE) for a hyperbolic double well potential (HDWP). We explore various values of the fractional derivative represented by k in our analysis. Our findings reveal intriguing behavior concerning the localization properties of the position entropy density, ρs(x), and the momentum entropy density, ρs(p), for low-lying states. Specifically, as the fractional derivative k decreases, ρs(x) becomes more localized, whereas ρs(p) becomes more delocalized. Moreover, we observe that as the derivative k decreases, the position entropy Sx decreases, while the momentum entropy Sp increases. In particular, the sum of these entropies consistently increases with decreasing fractional derivative k. It is noteworthy that, despite the increase in position Shannon entropy Sx and the decrease in momentum Shannon entropy Sp with an increase in the depth u of the HDWP, the Beckner–Bialynicki-Birula–Mycielski (BBM) inequality relation remains satisfied. Furthermore, we examine the Fisher entropy and its dependence on the depth u of the HDWP and the fractional derivative k. Our results indicate that the Fisher entropy increases as the depth u of the HDWP is increased and the fractional derivative k is decreased.
On the Applicability of Quantum Machine Learning
Authors: Raubitzek Sebastian , Mallinger Kevin
Published: June 2023

In this article, we investigate the applicability of quantum machine learning for classification tasks using two quantum classifiers from the Qiskit Python environment: the variational quantum circuit and the quantum kernel estimator (QKE). We provide a first evaluation on the performance of these classifiers when using a hyperparameter search on six widely known and publicly available benchmark datasets and analyze how their performance varies with the number of samples on two artificially generated test classification datasets. As quantum machine learning is based on unitary transformations, this paper explores data structures and application fields that could be particularly suitable for quantum advantages. Hereby, this paper introduces a novel dataset based on concepts from quantum mechanics using the exponential map of a Lie algebra. This dataset will be made publicly available and contributes a novel contribution to the empirical evaluation of quantum supremacy. We further compared the performance of VQC and QKE on six widely applicable datasets to contextualize our results. Our results demonstrate that the VQC and QKE perform better than basic machine learning algorithms, such as advanced linear regression models (Ridge and Lasso). They do not match the accuracy and runtime performance of sophisticated modern boosting classifiers such as XGBoost, LightGBM, or CatBoost. Therefore, we conclude that while quantum machine learning algorithms have the potential to surpass classical machine learning methods in the future, especially when physical quantum infrastructure becomes widely available, they currently lag behind classical approaches. Our investigations also show that classical machine learning approaches have superior performance classifying datasets based on group structures, compared to quantum approaches that particularly use unitary processes. Furthermore, our findings highlight the significant impact of different quantum simulators, feature maps, and quantum circuits on the performance of the employed quantum estimators. This observation emphasizes the need for researchers to provide detailed explanations of their hyperparameter choices for quantum machine learning algorithms, as this aspect is currently overlooked in many studies within the field. To facilitate further research in this area and ensure the transparency of our study, we have made the complete code available in a linked GitHub repository.
Study of Energy Loss Characteristics of a Shaft Tubular Pump Device Based on the Entropy Production Method
Authors: Ji Dongtao , Lu Weigang , Xu Bo , Xu Lei , Lu Linguang
Published: June 2023

The unstable flow of a shaft tubular pump device (STPD) leads to energy loss, thereby reducing its efficiency. The aim of this study is to investigate the distribution pattern of energy loss in STPDs. This paper reveals that the two components with the highest proportion of energy loss are the impeller and the outlet passage. Furthermore, turbulent entropy production is the primary cause of energy loss. Due to the wall effect, the energy loss in the impeller mainly occurs near the hub and shroud. Additionally, the presence of a tip leakage vortex near the shroud further contributes to the energy loss in the region near the shroud. This results in the energy loss proportion exceeding 40% in the region with a volume fraction of 14% near the shroud. In the outlet passage, the energy loss mainly occurs in the front region, with a volume fraction of 30%, and the energy loss in this part accounts for more than 65%. Finally, this study reveals the locations of the vortex in the STPD under different flow-rate conditions, and when the distribution of energy loss is visualized, it is found that the energy loss occurs high in the vortex regions.
Optimal Reactive Power Dispatch in Electric Transmission Systems Using the Multi-Agent Model with Volt-VAR Control
Authors: Chamba Alex , Barrera-Singaña Carlos , Arcos Hugo
Published: June 2023

The optimal dispatch of reactive power is a fundamental task in the operational planning of electrical power systems. This task aims to minimize active power losses and improve voltage levels within the electrical power system. This paper presents the application of the particle swarm optimization methodology to achieve optimal reactive power dispatch. The methodology’s performance is demonstrated by its high processing speed and the results obtained through a comprehensive global search for reactive power dispatch. Additionally, experimental results confirm the algorithm’s effectiveness in optimizing the objective function across different case studies, highlighting its ability to achieve optimal reactive power dispatch. This study represents a significant advancement in the field of power system optimization and provides a useful tool for managing and controlling these systems.
Theoretical Analysis of the Effect of Electrical Heat In Situ Injection on the Kerogen Decomposition for the Development of Shale Oil Deposits
Authors: Briceño Montilla Maryelin Josefina , Li Shouding , Zhang Zhaobin , Li Xiao , Sun Yiming , Ma Shiwei
Published: June 2023

In situ heat injection is a suitable technique for extracting shale oil from reservoirs with high organic matter content but insufficient thermal maturation. To optimize the stimulation process and to avoid unnecessary energy consumption, understanding the thermal process and the effects of thermal parameters is crucial. This research employs a self-developed simulator to build a 2D numerical model of the in situ conversion process of kerogen with electric heaters. A benchmark model is first established to determine the effects of heat injection on crude oil production and kerogen decomposition. Subsequently, this study analyzes the evolution of shale oil within the reservoir, identifying the role of thermal and physical properties in crude oil production and kerogen decomposition during the stimulation treatment. A sensitivity analysis of the thermal properties of the reservoir is also carried out, which allows for defining the role of the thermal conductivity of the rock during the stimulation process. Finally, it is observed that, when using the injection at a constant power, the injection time to achieve a suitable large rate of decomposition is shorter than at a constant temperature—consequently, it has a higher economic advantage.
Hydraulic Fracture Propagation and Proppant Transport Mechanism in Interlayered Reservoir
Authors: Wang Jue , Peng Genbo , Cong Ziyuan , Hu Buqin
Published: June 2023

Hydraulic fracture is crucial for assuring well production from unconventional reservoirs. For the optimization of hydraulic fracture geometry and the ensuing production of an interlayered reservoir, vertical hydraulic fracture propagation path has been analyzed. However, an effective fluid channel cannot be formed if the proppant is unable to reach the area where the fracture propagates. This paper presents a numerical model using the lattice-based method to investigate the hydraulic fracture propagation and proppant transport mechanism in interlayered reservoirs. The hydraulic fracture propagation model was simulated under different geological and fracturing engineering factors. The results indicate that interlayer Young’s modulus and horizontal stress anisotropy are positively correlated with longitudinal propagation and proppant carrying ability in interlayered formations. The fracturing injection rate has an optimal solution for fracture propagation and proppant carrying since a too low injection rate is unfavorable for fracture penetration of the interlayer, while a too high injection rate increases fracture width instead of further fracture penetration. In conclusion, attention is drawn to fine particle size proppants used in multi-layer reservoirs for fracturing fluid to carry proppants as far as possible to obtain maximum propped area.
Optimal Demand Response Using Battery Storage Systems and Electric Vehicles in Community Home Energy Management System-Based Microgrids
Authors: Abbasi Ayesha , Sultan Kiran , Afsar Sufyan , Aziz Muhammad Adnan , Khalid Hassan Abdullah
Published: June 2023

Demand response (DR) strategies are recieving much attention recently for their applications in the residential sector. Electric vehicles (EVs), which are considered to be a fairly new consumer load in the power sector, have opened up new opportunities by providing the active utilization of EVs as a storage unit. Considering their storage capacities, they can be used in vehicle-to-grid (V2G) or vehicle-to-community (V2C) options instead of taking power in peak times from the grid itself. This paper suggests a community-based home energy management system for microgrids to achieve flatter power demand and peak demand shaving using particle swarm optimization (PSO) and user-defined constraints. A dynamic clustered load scheduling scheme is proposed, including a method for managing peak shaving using rules specifically designed for PV systems that are grid-connected alongside battery energy storage systems and electric vehicles. The technique being proposed involves determining the limits of feed-in and demand dynamically, using estimated load demands and profiles of PV power for the following day. Additionally, an optimal rule-based management technique is presented for the peak shaving of utility grid power that sets the charge/discharge schedules of the battery and EV one day ahead. Utilizing the PSO algorithm, the optimal inputs for implementing the rule-based peak shaving management strategy are calculated, resulting in an average improvement of about 7% in percentage peak shaving (PPS) when tested using MATLAB for numerous case studies.
Thermomodernization as a Mechanism for Improving Energy Efficiency and Reducing Emissions of Pollutants into the Atmosphere in a Public Utility Building
Authors: Szczotka Krzysztof , Barwińska-Małajowicz Anna , Szymiczek Jakub , Pyrek Radosław
Published: June 2023

Improving energy efficiency indicators and reasonable use of energy resources in the context of the increasing demand for energy are sectors that must definitely be paid attention to. The fight against climate change must start in the construction sector, as buildings are the main consumers of energy. Saving energy through the rational use of energy sources and good thermal insulation of buildings allows you to reduce the amount of heating and/or cooling bills as well as to care for the environment by reducing emissions. This article presents aspects of improving the energy efficiency of a health clinic building in Mszana Dolna through the use of comprehensive thermal modernization of the external envelope. Thermal modernization of the most energy-intensive and leaky external partitions in the building, i.e., the external walls below and above the ground and the ventilated flat roof, managed to save 53% of the building’s thermal energy, which directly translates into lowering the building’s operating costs. We managed to achieve an improvement in energy efficiency ratios from 37% to almost 60%, and a reduction in CO2 emissions at a level of nearly 50%.
Treatment of Effluent Containing p-Cresol through an Advanced Oxidation Process in a Batch Reactor: Kinetic Optimization
Authors: Oliveira Julierme G. C. , Brandão Yana B. , Oliveira Dinaldo C. , Teodosio Jailson R. , Moraes Cristiane M. , Converti Attilio , Casazza Alessandro Alberto , Sarubbo Leonie Asfora , Benachour Mohand
Published: June 2023

The present research is related to the study of p-cresol oxidation reaction in aqueous phase. Firstly, the conventional advanced oxidation process (AOP) in a lab-scale batch reactor was used, seeking to identify the most impacting process variables and then to propose an optimization approach for ensuring the complete p-cresol degradation and the highest total organic carbon (TOC) conversion. In the AOP with the use of hydrogen peroxide as the oxidizing agent, the oxidation reaction was optimized with the aid of a factorial design, and a maximum TOC conversion of 63% was obtained. The Lumped Kinetic Model (LKM) was used to describe the profile of residual TOC concentration due to chemical species, which were categorized into two groups (refractory and non-refractory compounds). The model was able to satisfactorily describe the profile of the residual fractions of these two classes of organic compounds and allowed estimating the related kinetic constants (k) at two different temperatures, namely (a) 3.19 × 10−1 and 2.82 × 10−3 min−1 for non-refractory and refractory compounds at 80 °C and (b) 4.73 × 10−1 and 5.09 × 10−3 min−1 for the same compound classes at 90 °C, while the activation energy (Ea) of the process was 42.02 and 62.09 kJ mol−1, respectively. The kinetic modeling of organic pollutants oxidation in liquid effluents would allow to perform in situ seawater treatment on vertical reactors installed in offshore platforms and to properly release treated water into the oceans. In this way, ocean contamination caused by the exploration on offshore platforms of oil and natural gas, the main energy sources and vectors in the current world, may be remarkably reduced, thus favoring a more eco-friendly energy production.
ARIMA Models in Solar Radiation Forecasting in Different Geographic Locations
Authors: Chodakowska Ewa , Nazarko Joanicjusz , Nazarko Łukasz , Rabayah Hesham S. , Abendeh Raed M. , Alawneh Rami
Published: June 2023

The increasing demand for clean energy and the global shift towards renewable sources necessitate reliable solar radiation forecasting for the effective integration of solar energy into the energy system. Reliable solar radiation forecasting has become crucial for the design, planning, and operational management of energy systems, especially in the context of ambitious greenhouse gas emission goals. This paper presents a study on the application of auto-regressive integrated moving average (ARIMA) models for the seasonal forecasting of solar radiation in different climatic conditions. The performance and prediction capacity of ARIMA models are evaluated using data from Jordan and Poland. The essence of ARIMA modeling and analysis of the use of ARIMA models both as a reference model for evaluating other approaches and as a basic forecasting model for forecasting renewable energy generation are presented. The current state of renewable energy source utilization in selected countries and the adopted transition strategies to a more sustainable energy system are investigated. ARIMA models of two time series (for monthly and hourly data) are built for two locations and a forecast is developed. The research findings demonstrate that ARIMA models are suitable for solar radiation forecasting and can contribute to the stable long-term integration of solar energy into countries’ systems. However, it is crucial to develop location-specific models due to the variability of solar radiation characteristics. This study provides insights into the use of ARIMA models for solar radiation forecasting and highlights their potential for supporting the planning and operation of energy systems.
Selection and Performance Prediction of a Pump as a Turbine for Power Generation Applications
Authors: Nasir Abdulbasit , Dribssa Edessa , Girma Misrak , Madessa Habtamu Bayera
Published: June 2023

The high price of purpose-made turbines always represents an active challenge when utilizing pico- and micro-hydropower resources. Pumps as turbines (PATs) are a promising option to solve the problem. However, the selection of a suitable pump for a specific site and estimating its performance in the reverse mode are both major problems in the field. Therefore, this paper aims to develop generic mathematical correlations between the site and the pump hydraulic data, which can be used to select the optimal operation of the pump as a turbine. A statistical model and the Pearson correlation coefficient formula were employed to generate correlations between the flow rate and the head of the pumps with the sites. Then, Ansys CFX, coupled with SST k-ω and standard k-ε turbulence models, was used to analyze the performance of the PAT. The analysis was conducted in terms of flow rate, pressure head, efficiency, and power output. The numerical results were validated using an experimental test rig. The deviations of the proposed correlations from the statistical model were found to be in the range of −0.2% and 1.5% for the flow rate and ±3.3% for the pressure head. The obtained numerical outputs using the standard k-ε turbulence model strongly agreed with the experimental results, with variations of −1.82%, 2.94%, 2.88%, and 1.76% for the flow rate, head, power, and efficiency, respectively. The shear stress transport (SST) k-ω turbulence model showed relatively higher deviations when compared to standard k-ε. From the results, it can be concluded that the developed mathematical correlations significantly contribute to selecting the optimal operation of the pump for power-generating applications. The adopted numerical procedure, selected mesh type, turbulence model, and physics setup provided good agreement with the test result. Among the two turbulence models, the standard k-ε performs better in estimating the pressure head, output power, and efficiency of the PAT with less than 3% errors when compared to experimental results.
A Rapid Method for Testing Filtration Performance of Malt and the Optimization of the Method
Authors: Sun Hairong , Zhang Yanqing , Hao Jianqin , Wang Deliang , Li Tao , Wang Minghao , Guo Qi
Published: June 2023

A rapid filtration test method that predicts malt filtration efficiency has been developed in this research. This rapid filtration test method has an advantage over existing beer filtration tests, as it can be easily operated and there is no need to brew. Six kinds of malts with distinct filtration performance were selected, and the filtration performance was determined by measuring the turbidity of their clarified wort through simple simulation of mashing. The results indicate the filtering performance ranking as given: Copeland > Pearl malt 1 > Pearl malt 2 > Synergy > Planet > Wheat malt. When a sample is purchased for six times of parallelization, RSD is less than 10%, and the experimental results are significantly correlated with viscosity and β-glucan content. Therefore, this method can effectively predict the filtration performance of malt. The response surface design 3 × 3 factor experiment was used to optimize the fast detection method, which increased the sample differentiation (F-value) and made it easier to judge the experimental results. Response surface experiment results show the optimal reaction conditions for enhancing differentiation, i.e., an enzyme ratio of 0.5 (α-amylase, β-glucanase, neutral protease = 1:2:1), a holding period of 38 min, and a reaction temperature of 44 °C. The F-value is 147.00.
Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature
Authors: Marinella Gemma , Orsini Alessandro , Scacciati Massimo , Costa Elisa , Santangelo Andrea , Astrea Guja , Frosini Silvia , Pasquariello Rosa , Rubegni Anna , Sgherri Giada , Corsi Martina , Bonuccelli Alice , Battini Roberta
Published: June 2023

Background: Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is CACNA1S, which is recognized as the cause of Dihydropyridine Receptor Congenital Myopathy. Methods: To better characterize the phenotypic spectrum of CACNA1S myopathy, we conducted a systematic review of cases in the literature through three electronic databases following the PRISMA guidelines. We selected nine articles describing 23 patients with heterozygous, homozygous, or compound heterozygous mutations in CACNA1S and we added one patient with a compound heterozygous mutation in CACNA1S (c.1394-2A>G; c.1724T>C, p.L575P) followed at our Institute. We collected clinical and genetic data, muscle biopsies, and muscle MRIs when available. Results: The phenotype of this myopathy is heterogeneous, ranging from more severe forms with a lethal early onset and mild–moderate forms with a better clinical course. Conclusions: Our patient presented a phenotype compatible with the mild–moderate form, although she presented peculiar features such as a short stature, myopia, mild sensorineural hearing loss, psychiatric symptoms, and posterior-anterior impairment gradient on thigh muscle MRI.
Potential Applications of Nanoparticles in Improving the Outcome of Lung Cancer Treatment
Authors: Girigoswami Agnishwar , Girigoswami Koyeli
Published: June 2023

Lung cancer is managed using conventional therapies, including chemotherapy, radiation therapy, or a combination of both. Each of these therapies has its own limitations, such as the indiscriminate killing of normal as well as cancer cells, the solubility of the chemotherapeutic drugs, rapid clearance of the drugs from circulation before reaching the tumor site, the resistance of cancer cells to radiation, and over-sensitization of normal cells to radiation. Other treatment modalities include gene therapy, immunological checkpoint inhibitors, drug repurposing, and in situ cryo-immune engineering (ICIE) strategy. Nanotechnology has come to the rescue to overcome many shortfalls of conventional therapies. Some of the nano-formulated chemotherapeutic drugs, as well as nanoparticles and nanostructures with surface modifications, have been used for effective cancer cell killing and radio sensitization, respectively. Nano-enabled drug delivery systems act as cargo to deliver the sensitizer molecules specifically to the tumor cells, thereby enabling the radiation therapy to be more effective. In this review, we have discussed the different conventional chemotherapies and radiation therapies used for inhibiting lung cancer. We have also discussed the improvement in chemotherapy and radiation sensitization using nanoparticles.
Knife Decontamination by Cold Water Treatment Supplemented with InspexxTM 210—A Validation Study in an Abattoir
Authors: Kelbert Lucien , Stephan Roger
Published: June 2023

To evaluate the decontamination effect of Inspexx 210, a cold-water disinfectant containing peracetic acid and peroctanoic acid (0.16%), knives contaminated with E. coli ATCC 25922 and S. aureus ATCC 29213 as well as naturally contaminated knives collected from different slaughtering steps of an abattoir were examined. Treatment with Inspexx 210 for 15 s reduced mean E. coli counts by 5.95 log CFU/cm2 and mean S. aureus counts by 6.24 log CFU/cm2. Contamination of the knives first with fat and thereafter with the bacteria led to lower mean reductions of 5.52 log CFU/cm2 for E. coli and 3.58 log CFU/cm2 for S. aureus. Contamination first with blood and thereafter with the bacteria had the greatest negative impact on the inactivation effect, with mean reductions of 3.70 log CFU/cm2 for E. coli and 1.55 log CFU/cm2 for S. aureus. Rinsing the blood with tap water before contamination with S. aureus led to the reduction of 5.50 log CFU/cm2. Treatment with Inspexx 210 was also assessed for naturally contaminated knives from an abattoir. After treatment under routine conditions, colony counts were 0.09 log CFU/cm2 (pigs) and 0.35 log CFU/cm2 (sheep) in the wet area and below detection limit (pigs) and 0.91 (sheep) in the clean area. This study shows that Inspexx 210 can be an adequate alternative to knife decontamination with 82 °C hot water, but pre-rinsing is recommended especially in dirty process steps with a high contamination of blood and fat.
Food Insecurity and Blood Pressure in a Multiethnic Population
Authors: Ing Claire Townsend , Clemens Brettany , Ahn Hyeong Jun , Kaholokula Joseph Keawe‘aimoku , Hovmand Peter S. , Seto Todd B. , Novotny Rachel
Published: June 2023

Food insecurity is a social determinant of health and is increasingly recognized as a risk factor for hypertension. Native Hawaiians bear a disproportionate burden of hypertension and known risk factors. Despite this, the relative effects of food insecurity and financial instability on blood pressure have yet to be investigated in this population. This study examines the relative effects of food insecurity and financial instability on blood pressure, controlling for potential confounders in a multiethnic sample. Participants (n = 124) were recruited from a U.S. Department of Agriculture-funded study called the Children’s Healthy Living Center of Excellence. Biometrics (i.e., blood pressure, weight, and height) were measured. Demographics, physical activity, diet, psychosocial variables, food insecurity, and financial instability were assessed via self-report questionnaires. Hierarchical linear regression models were conducted. Model 1, which included sociodemographic variables and known biological risk factors, explained a small but significant amount of variance in systolic blood pressure. Model 2 added physical activity and daily intake of fruit, fiber, and whole grains, significantly improving the model. Model 3 added financial instability and food insecurity, further improving the model (R2 = 0.37, F = 2.67, p = 0.031). Food insecurity, female sex, and BMI were significantly and independently associated with increased systolic blood pressure. These results suggest a direct relationship between food insecurity and systolic blood pressure, which persisted after controlling for physical activity, consumption of fruits, fiber, and whole grains, and BMI. Efforts to reduce food insecurity, particularly among Native Hawaiians, may help reduce hypertension in this high-risk population.
Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques
Authors: Caruso Francesco , Rossi Miriam , Eberhardt Eric , Berinato Molly , Sakib Raiyan , Surco-Laos Felipe , Chavez Haydee
Published: June 2023

The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body’s endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone’s other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L’Héritier) DC.
Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
Authors: Agulló Laura , Aguado Isidro , Muriel Javier , Margarit César , Gómez Alba , Escorial Mónica , Sánchez Astrid , Fernández Alicia , Peiró Ana M.
Published: June 2023

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1–5] vs. 1 [0–2], p < 0.01) and 42% opioid dose (35 [22–61] vs. 60 [40–80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58–0.82] vs. 0.51 [0.13–0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.
Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders
Authors: D’Antoni Chiara , Mautone Lorenza , Sanchini Caterina , Tondo Lucrezia , Grassmann Greta , Cidonio Gianluca , Bezzi Paola , Cordella Federica , Di Angelantonio Silvia
Published: June 2023

Understanding the complexities of the human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations in replicating its intricacies, necessitating the development of in vitro models that can simulate its structure and function. Three-dimensional in vitro models, including organoids, cerebral organoids, bioprinted brain models, and functionalized brain organoids, offer promising platforms for studying human brain development, physiology, and disease. These models accurately replicate key aspects of human brain anatomy, gene expression, and cellular behavior, enabling drug discovery and toxicology studies while providing insights into human-specific phenomena not easily studied in animal models. The use of human-induced pluripotent stem cells has revolutionized the generation of 3D brain structures, with various techniques developed to generate specific brain regions. These advancements facilitate the study of brain structure development and function, overcoming previous limitations due to the scarcity of human brain samples. This technical review provides an overview of current 3D in vitro models of the human cortex, their development, characterization, and limitations, and explores the state of the art and future directions in the field, with a specific focus on their applications in studying neurodevelopmental and neurodegenerative disorders.
Establishment and Characterization of Free-Floating 3D Macrophage Programming Model in the Presence of Cancer Cell Spheroids
Authors: Korotkaja Ksenija , Jansons Juris , Spunde Karina , Rudevica Zhanna , Zajakina Anna
Published: June 2023

Reprogramming of tumor-associated macrophages (TAMs) is a promising strategy for cancer immunotherapy. Several studies have shown that cancer cells induce/support the formation of immunosuppressive TAMs phenotypes. However, the specific factors that orchestrate this immunosuppressive process are unknown or poorly studied. In vivo studies are expensive, complex, and ethically constrained. Therefore, 3D cell interaction models could become a unique framework for the identification of important TAMs programming factors. In this study, we have established and characterized a new in vitro 3D model for macrophage programming in the presence of cancer cell spheroids. First, it was demonstrated that the profile of cytokines, chemokines, and surface markers of 3D-cultured macrophages did not differ conceptually from monolayer-cultured M1 and M2-programmed macrophages. Second, the possibility of reprogramming macrophages in 3D conditions was investigated. In total, the dynamic changes in 6 surface markers, 11 cytokines, and 22 chemokines were analyzed upon macrophage programming (M1 and M2) and reprogramming (M1→M2 and M2→M1). According to the findings, the reprogramming resulted in a mixed macrophage phenotype that expressed both immunosuppressive and anti-cancer immunostimulatory features. Third, cancer cell spheroids were shown to stimulate the production of immunosuppressive M2 markers as well as pro-tumor cytokines and chemokines. In summary, the newly developed 3D model of cancer cell spheroid/macrophage co-culture under free-floating conditions can be used for studies on macrophage plasticity and for the development of targeted cancer immunotherapy.
Gene Therapy Approaches for the Treatment of Hemophilia B
Authors: Soroka Anastasiia B. , Feoktistova Sofya G. , Mityaeva Olga N. , Volchkov Pavel Y.
Published: June 2023

In contrast to the standard enzyme-replacement therapy, administered from once per 7–14 days to 2–3 times a week in patients with severe hemophilia B, as a result of a single injection, gene therapy can restore F9 gene expression and maintain it for a prolonged time. In clinical research, the approach of delivering a functional copy of a gene using adeno-associated viral (AAV) vectors is widely used. The scientific community is actively researching possible modifications to improve delivery efficiency and expression. In preclinical studies, the possibility of genome editing using CRISPR/Cas9 technology for the treatment of hemophilia B is also being actively studied.
Comparative Study of Terminal Cortical Potentials Using Iridium and Ag/AgCl Electrodes
Authors: Mingazov Bulat , Vinokurova Daria , Zakharov Andrei , Khazipov Roustem
Published: June 2023

Brain ischemia induces slow voltage shifts in the cerebral cortex, including waves of spreading depolarization (SD) and negative ultraslow potentials (NUPs), which are considered as brain injury markers. However, different electrode materials and locations yield variable SD and NUP features. Here, we compared terminal cortical events during isoflurane or sevoflurane euthanasia using intracortical linear iridium electrode arrays and Ag/AgCl-based electrodes in the rat somatosensory cortex. Inhalation of anesthetics caused respiratory arrest, associated with hyperpolarization and followed by SD and NUP on both Ir and Ag electrodes. Ag-NUPs were bell shaped and waned within half an hour after death. Ir-NUPs were biphasic, with the early fast phase corresponding to Ag-NUP, and the late absent on Ag electrodes, phase of a progressive depolarizing voltage shift reaching −100 mV by two hours after death. In addition, late Ir-NUPs were more ample in the deep layers than at the cortical surface. Thus, intracortical Ag and Ir electrodes reliably assess early manifestations of terminal brain injury including hyperpolarization, SD and the early phase of NUP, while the late, giant amplitude phase of NUP, which is present only on Ir electrodes, is probably related to the sensitivity of Ir electrodes to a yet unidentified factor related to brain death.
Homocysteine and Glaucoma
Authors: Washington Joshua , Ritch Robert , Liu Yutao
Published: June 2023

Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous system. Defects in Hcy metabolism have been associated with many neurodegenerative diseases including glaucoma, i.e., the leading cause of blindness. However, the pathophysiology of elevated Hcy and its eligibility as a risk factor for glaucoma remain unclear. We aimed to provide a comprehensive review of the relationship between elevated Hcy levels and glaucoma. Through a systemic search of the PubMed and Google Scholar databases, we found that elevated Hcy might play an important role in the pathogenesis of glaucoma. Further research will be necessary to help clarify the specific contribution of elevated Hcy in the pathogenesis of glaucoma. A discovery and conceptual understanding of Hcy-associated glaucoma could be the keys to providing better therapeutic treatment, if not prophylactic treatment, for this disease.
Metagenome of Gut Microbiota Provides a Novel Insight into the Pathogenicity of Balantioides coli in Weaned Piglets
Authors: He Kai , Xiong Jie , Yang Wentao , Zhao Lizhuo , Wang Tianqi , Qian Weifeng , Hu Suhui , Wang Qiangqiang , Aleem Muhammad Tahir , Miao Wei , Yan Wenchao
Published: June 2023

Balantioides coli plays an important role in the diarrhea of weaned piglets, but its pathogenic potential and interaction with gut microbes remain unclear. To investigate the impact of B. coli colonization on the gut bacterial structure and function of weaned piglets, a metagenomic analysis based on shotgun sequencing was performed on fresh fecal samples collected from ten B. coli-colonized piglets and eight B. coli-free ones in this study. The results showed that decreasing diversity and shifted composition and function of the bacterial community were detected in the weaned piglets infected by B. coli. In contrast to the B. coli-negative group, the relative abundances of some members of the Firmicutes phylum including Clostridium, Ruminococcus species, and Intestinimonas butyriciproducens, which produce short-chain fatty acids, were significantly reduced in the B. coli-positive group. Notably, some species of the Prevotella genus (such as Prevotella sp. CAG:604 and Prevotella stercorea) were significantly increased in abundance in the B. coli-positive piglets. A functional analysis of the gut microbiota demonstrated that the differential gene sets for the metabolism of carbohydrates and amino acids were abundant in both groups, and the more enriched pathways in B. coli-infected piglets were associated with the sugar-specific phosphotransferase system (PTS) and the two-component regulatory system, as well as lipopolysaccharide (LPS) biosynthesis. Furthermore, several species of Prevotella were significantly positively correlated to the synthesis of lipid A, leading to the exporting of endotoxins and, thereby, inducing inflammation in the intestines of weaned piglets. Taken together, these findings revealed that colonization by B. coli was distinctly associated with the dysbiosis of gut bacterial structure and function in weaned piglets. Lower relative abundances of Clostridiaceae and Ruminococcaceae and higher abundances of Prevotella species were biomarkers of B. coli infection in weaned piglets.
Health Effects of Natural Antioxidants
Authors: Boccellino Mariarosaria
Published: June 2023

Free radicals are produced during metabolic processes in the human body and can lead to oxidative stress, cellular aging, and the development of various diseases [...]
The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke
Authors: Chou Ping-Song , Yang I-Hsiao , Kuo Chia-Ming , Wu Meng-Ni , Lin Tzu-Chao , Fong Yi-On , Juan Chi-Hung , Lai Chiou-Lian
Published: June 2023

Bidirectional communication of the microbiota–gut–brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0–3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.
Vps4a Regulates Autophagic Flux to Prevent Hypertrophic Cardiomyopathy
Authors: Huang Xiaozhi , Zhang Jiayin , Wang Wenyi , Huang Zhishan , Han Peidong
Published: June 2023

Autophagy has stabilizing functions for cardiomyocytes. Recent studies indicate that an impairment in the autophagy pathway can seriously affect morphology and function, potentially leading to heart failure. However, the role and the underlying mechanism of the endosomal sorting complex required for transport (ESCRT) family protein, in particular the AAA-ATPase vacuolar protein sorting 4a (Vps4a), in regulating myocardial autophagy remains unclear. In the present study, cardiomyocyte-specific Vps4a knockout mice were generated by crossing Vps4aflox/flox (Vps4afl/fl) with Myh6-cre transgenic mice. As a result, we observed a partially dilated left ventricular (LV) chamber, a significant increase in heart weight to body weight ratio (HW/BW), and heart weight to tibial length ratio (HW/TL), hypertrophic cardiomyopathy and early lethality starting at 3 months of age. Hematoxylin-eosin (HE), immunofluorescence assay (IFA), and Western blot (WB) revealed autophagosome accumulation in cardiomyocytes. A transcriptome-based analysis and autophagic flux tracking by AAV-RFP-GFP-LC3 showed that the autophagic flux was blocked in Vps4a knockout cardiomyocytes. In addition, we provided in vitro evidence demonstrating that Vps4a and LC3 were partially co-localized in cardiomyocytes, and the knockdown of Vps4a led to the accumulation of autophagosomes in cardiomyocytes. Similarly, the transfection of cardiomyocytes with adenovirus (Adv) mCherry-GFP-LC3 further indicated that the autophagic flux was blocked in cells with deficient levels of Vps4a. Finally, an electron microscope (EM) showed that the compromised sealing of autophagosome blocked the autophagic flux in Vps4a-depleted cardiomyocytes. These findings revealed that Vps4a contributed to the sealing of autophagosomes in cardiomyocytes. Therefore, we demonstrated that Vps4a deletion could block the autophagic flux, leading to the accumulation of degradation substances and compromised cardiac function. Overall, this study provides insights into a new theoretical basis for which autophagy may represent a therapeutic target for cardiovascular diseases.
Transcriptomic and Metabolomic Analyses Provide Insights into the Pathogenic Mechanism of the Rice False Smut Pathogen Ustilaginoidea virens
Authors: Fu Rongtao , Wang Jian , Chen Cheng , Liu Yao , Zhao Liyu , Lu Daihua
Published: June 2023

Rice false smut, caused by the fungal pathogen Ustilaginoidea virens, is a worldwide rice fungal disease. However, the molecular mechanism of the pathogenicity of the fungus U. virens remains unclear. To understand the molecular mechanism of pathogenesis of the fungus U. virens, we performed an integrated analysis of the transcriptome and metabolome of strongly (S) and weakly (W) virulent strains both before and after the infection of panicles. A total of 7932 differential expressed genes (DEGs) were identified using transcriptome analysis. Gene ontology (GO) and metabolic pathway enrichment analysis indicated that amino acid metabolism, autophagy-yeast, MAPK signaling pathway-yeast, and starch and sucrose metabolism were closely related to the pathogenicity of U. virens. Genes related to pathogenicity were significantly upregulated in the strongly virulent strain, and were ATG, MAPK, STE, TPS, and NTH genes. However, genes involved in the negative regulation of pathogenesis were significantly downregulated and contained TOR kinase, TORC1, and autophagy-related protein genes. Metabolome analysis identified 698 differentially accumulated metabolites (DAMs), including 13 categories of organic acids and derivatives, lipids and lipid-like molecules, organoheterocyclic compounds. The significantly enriched pathways of DAMs mainly included amino acids and carbohydrates, and they accumulated after infection by the S strain. To understand the relevance of DEGs and DAMs in the pathogenicity of U. virens, transcriptomic and metabolomic data were integrated and analyzed. These results further confirmed that the pathogenesis of U. virens was regulated by DEGs and DAMs related to these four pathways, involving arginine and proline metabolism, lysine biosynthesis, alanine, aspartate and glutamate metabolism, and starch and sugar metabolism. Therefore, we speculate that the pathogenicity of U. virens is closely related to the accumulation of amino acids and carbohydrates, and to the changes in the expression of related genes.