bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Myocardial Perfusion Scintigraphy and Coronary Angiography Results in Breast Cancer Patients Treated with Radiotherapy
Authors: Özkan Uğur , Gürdoğan Muhammet
Published: April 2023

Breast cancer is the most common type of malignancy in women and radiotherapy (RT) is an important part of treatment. Although it reduces cancer recurrence, it has been shown to cause accerelerated athnerosclerosis. This study aimed to compare the results of myocardial perfusion scintigraphy (MPS) for ischemia investigation with coronary angiography (CAG) findings and to investigate the effect of RT on the development of coronary artery disease in breast cancer patients who underwent RT. The results of 660 patients were analyzed and compared with each other in terms of clinical, demographic, laboratory parameters and MPS results. The mean age was 57.5 years and all of them were female. When the groups were compared, the Gensini score and marking of the left anterior descending artery (LAD) area as ischemic area localization were found more, but angiographically, the rate of severe stenosis in the area indicated by MPS was found to be lower in the RT group (p < 0.001). While the sensitivity of MPS in the RT group was 67.5% and non-RT group was 88.5% (p < 0.001), the result of our study shows that the sensitivity of the MPS test is significantly lower in the patient group receiving RT.
Link Prediction with Continuous-Time Classical and Quantum Walks
Authors: Goldsmith Mark , Saarinen Harto , García-Pérez Guillermo , Malmi Joonas , Rossi Matteo A. C. , Maniscalco Sabrina
Published: April 2023

Protein–protein interaction (PPI) networks consist of the physical and/or functional interactions between the proteins of an organism, and they form the basis for the field of network medicine. Since the biophysical and high-throughput methods used to form PPI networks are expensive, time-consuming, and often contain inaccuracies, the resulting networks are usually incomplete. In order to infer missing interactions in these networks, we propose a novel class of link prediction methods based on continuous-time classical and quantum walks. In the case of quantum walks, we examine the usage of both the network adjacency and Laplacian matrices for specifying the walk dynamics. We define a score function based on the corresponding transition probabilities and perform tests on six real-world PPI datasets. Our results show that continuous-time classical random walks and quantum walks using the network adjacency matrix can successfully predict missing protein–protein interactions, with performance rivalling the state-of-the-art.
A Resource-Adaptive Routing Scheme with Wavelength Conflicts in Quantum Key Distribution Optical Networks
Authors: Zhao Tao , Fan Xiaodong , Dong Bowen , Niu Quanhao , Guo Banghong
Published: April 2023

Quantum key distribution (QKD) has great potential in ensuring data security. Deploying QKD-related devices in existing optical fiber networks is a cost-effective way to practically implement QKD. However, QKD optical networks (QKDON) have a low quantum key generation rate and limited wavelength channels for data transmission. The simultaneous arrival of multiple QKD services may also lead to wavelength conflicts in QKDON. Therefore, we propose a resource-adaptive routing scheme (RAWC) with wavelength conflicts to achieve load balancing and efficient utilization of network resources. Focusing on the impact of link load and resource competition, this scheme dynamically adjusts the link weights and introduces the wavelength conflict degree. Simulation results indicate that the RAWC algorithm is an effective approach to solving the wavelength conflict problem. Compared with the benchmark algorithms, the RAWC algorithm can improve service request success rate (SR) by up to 30%.
Nuclear Power Plant to Support Indonesia’s Net Zero Emissions: A Case Study of Small Modular Reactor Technology Selection Using Technology Readiness Level and Levelized Cost of Electricity Comparing Method
Authors: Rahmanta Mujammil Asdhiyoga , Harto Andang Widi , Agung Alexander , Ridwan Mohammad Kholid
Published: April 2023

Most power plants, particularly those that burn fossil fuels such as coal, oil, and gas, create CO2, a greenhouse gas that contributes to climate change. By 2060, the Indonesian government has committed to reach net zero emissions. With the lowest CO2 emissions, nuclear power plants are dependable sources of energy. Small modular reactors (SMRs) are a particular kind of nuclear power plant that has the potential to be Indonesia’s first commercial nuclear power plant because of their small size, low capacity, uncomplicated design, and modular characteristics. The purpose of this study is to examine the economics and technological feasibility of SMRs. In this analysis, the levelized cost of electricity (LCOE) comparative method and the technology readiness level (TRL) approach are both applied. The SMRs with a minimum TRL value of 7 were CAREM-25 (TRL7), KLT-40S (TRL8), and HTR-PM (TRL 8), according to the results of this research. Although CAREM-25 and KLT-40S are still in the demonstration stage and have not yet entered the market, their LCOE estimates are greater than 0.07 USD/kWh with a 5% discount rate. Whereas CAREM 100 MW is an economy scale from CAREM-25 and VBER 300 MW is a commercial size from KLT-40S, HTR-PM is already an economy scale. With discount rates between 5% and 10%, the LCOE values of HTR-PM, CAREM 100 MW, and VBER 300 MW range from 0.06 USD to 0.12 USD per kWh. Other than hydropower and coal-fired power plants, these LCOE figures can compete with the local LCOE in Indonesia and the LCOE of a variety of other types of power plants.
Structure-Circuit Resistor Integrated Design Optimization of Piezoelectric Energy Harvester Considering Stress Constraints
Authors: Kim Taekyun , Kim Jihoon , Lee Tae Hee
Published: April 2023

A piezoelectric energy harvester (PEH) transduces mechanical energy into electrical energy, which can be utilized as an energy source for self-powered or low-power devices. Therefore, maximizing the power of a PEH is a crucial design objective. It is well known that structural designs are firstly conducted for controlling resonance characteristics, and then circuit designs are pursued through impedance matching for improving power. However, a PEH contains solid mechanics, electrostatics, and even a circuit-coupled multi-physics system. Therefore, this research aims to design a PEH considering a circuit-coupled multi-physics. As a design process, a conceptual design is developed by topology optimization, and a detailed design is developed sequentially by applying size optimization as a post-processing step to refine the conceptual design results for manufacturable design. In the two optimization processes, design optimizations of a structure coupled with circuit resistor are performed to maximize the power, where the electrical and mechanical interactions between PZT, substrate, and circuit resistor are simultaneously considered. Additionally, stress constraints are also added for structural safety to ensure operational life of PEH. As a result of the proposed design methodology, a manufacturable design of PEH having maximum power and operational life is obtained with power density of 6.61 μWg−2mm−3.
The Influence of Water Temperature on the Hydrogeochemical Composition of Groundwater during Water Extraction and Reinjection with Geothermal Heat
Authors: Verbovšek Timotej
Published: April 2023

This study presents a simulation of potential changes in groundwater in three wells within a Quaternary gravel aquifer in the city of Ljubljana when groundwater cooled by about 4 °C is reinjected into it. The research focuses on the mass transport of calcite in the vicinity of boreholes. According to our results, the impact of the changes in the geochemical composition of the water is relatively small (around 1%). Although the waters are approximately in equilibrium, calcite may be dissolved and sometimes precipitated within the aquifer when cooled water is reinjected into it. The amounts of precipitated calcite always decrease with decreasing temperatures of the reinjected water, which can lead to calcite dissolution if the temperature difference is large enough and the water is only slightly oversaturated. This novel finding is significant since previously published studies have mostly focused on understanding the scaling (precipitation) of calcite and not its dissolution. The mass transfer of calcite is relatively low, but in a scenario of long-term pumping for several years, such low values could lead to a dissolved or precipitated mass of several hundreds of kilograms of calcite per year (at a pumping rate of 46 L/s).
Characterization of Thermophysical and Electrical Properties of SiC and BN Nanofluids
Authors: Ajeeb Wagd , Murshed S. M. Sohel
Published: April 2023

Experimental data associated with the thermophysical properties (TPPs) of various nanofluids (NFs) are essential for their diverse applications in energy storage and conversion, as well as thermal management. This study experimentally investigated important TPPs such as thermal conductivity (TC), thermal diffusivity, density and viscosity, as well as the electrical conductivity of two new types of NFs, namely silica (SiC) and boron nitride (BN) nanofluids. The NFs are prepared at five low concentrations of nanoparticles from 0.01 to 0.05 vol.% dispersed into a mixture of ethylene glycol (EG) and distilled water (DW). The TPPs are measured, and their enhancements are evaluated in comparison with their base fluids. The results show a good increase in TC and thermal diffusivity for both types of nanofluids with increasing concentrations until reaching the maximum enhancement of about 4.4% for the SiC nanofluid and about 7.0% for the BN nanofluid at the same concentration (0.05 vol.%). On other hand, a Newtonian rheological behaviour is observed, and viscosity and density are also found to increase for both types of NFs, where the maximum increase in viscosity and density at 0.05 vol.% are found to be 5.2% and 0.3%, respectively. The electrical conductivity also increases by up to 3.2 times for SiC nanofluids and 2.8 times for BN nanofluids at the maximum concentration of these nanoparticles (0.05 vol.%) compared with the base fluid (EG/DW). The overall evaluation of the obtained results demonstrates the great potential of these nanofluids in heat transfer applications.
Climate Benefits Advocated by the Development of Sustainable Vehicles and Charging Infrastructures in the Transport Sector
Authors: Ventura José A.
Published: April 2023

Sustainable transportation refers to low vehicular greenhouse gas (GHG) emissions, energy efficient vehicles, and affordable modes of transportation, including electric and alternative fuel (AF) vehicles [...]
WT-YOLOX: An Efficient Detection Algorithm for Wind Turbine Blade Damage Based on YOLOX
Authors: Yao Yuan , Wang Guozhong , Fan Jinhui
Published: April 2023

Wind turbine blades will suffer various surface damages due to their operating environment and high-speed rotation. Accurate identification in the early stage of damage formation is crucial. The damage detection of wind turbine blades is a primarily manual operation, which has problems such as high cost, low efficiency, intense subjectivity, and high risk. The rise of deep learning provides a new method for detecting wind turbine blade damage. However, in detecting wind turbine blade damage in general network models, there will be an insufficient fusion of multiscale small target features. This paper proposes a lightweight cascaded feature fusion neural network model based on YOLOX. Firstly, the lightweight area of the backbone feature extraction network concerning the RepVGG network structure is enhanced, improving the model’s inference speed. Second, a cascaded feature fusion module is designed to cascade and interactively fuse multilevel features to enhance the small target area features and the model’s feature perception capabilities for multiscale target damage. The focal loss is introduced in the post-processing stage to enhance the network’s ability to learn complex positive sample damages. The detection accuracy of the improved algorithm is increased by 2.95%, the mAP can reach 94.29% in the self-made dataset, and the recall rate and detection speed are slightly improved. The experimental results show that the algorithm can autonomously learn the blade damage features from the wind turbine blade images collected in the actual scene, achieve the automatic detection, location, and classification of wind turbine blade damage, and promote the detection of wind turbine blade damage towards automation, rapidity, and low-cost development.
Overview of Energy Harvesting Technologies Used in Road Vehicles
Authors: Caban Jacek , Vrabel Jan , Górnicka Dorota , Nowak Radosław , Jankiewicz Maciej , Matijošius Jonas , Palka Marek
Published: April 2023

Road transport is one of the most important factors for the national economy due to its universality and comprehensive possibilities of transporting people and goods. Unfortunately, from the energy point of view, it is also the most cost-intensive and has a negative influence on the natural environment. For these reasons, issues related to limiting the use of conventional fuels are very important, which results in reducing emissions from this sector, as well as reducing transport costs. This article presents currently used energy sources for propulsion of road vehicles, including fossil and alternative fuels, gaseous fuels and other energy sources such as fuel cells. The following section presents technologies that allow to recover some of the energy lost in motor vehicles and internal combustion engines used for their propulsion. The principle of operation of these solutions, their structure and their main features are presented. The last part focuses on discussing and identifying the most universal technologies for energy harvesting in vehicles and showing further directions of energy development in the automotive sector.
Calorific Value of Zea mays Biomass Derived from Soil Contaminated with Chromium (VI) Disrupting the Soil’s Biochemical Properties
Authors: Wyszkowska Jadwiga , Borowik Agata , Zaborowska Magdalena , Kucharski Jan
Published: April 2023

One of the major challenges faced by contemporary agriculture is how to achieve better yields of crops and, consequently, higher biomass, even in unfavorable environmental conditions. This challenge corresponds to the assumptions of sustainable development, wherein it is envisaged that plant biomass should be used on a large scale for heat generation or conversion of biofuels. Keeping pace with observed trends, the following study was conducted in order to determine the effect of Cr(VI) on the net calorific value of Zea mays, to assess the impact of this element on soil enzymatic activity, and to identify the effectiveness of compost and humic acids in alleviating possible negative effects of Cr(VI) toxicity. These aims were pursued by setting up a pot experiment, in which soil either uncontaminated or contaminated with increasing doses of Cr(VI) of 0, 15, 30, 45, and 60 mg Cr kg−1 d.m. was submitted to biostimulation with compost and the preparation HumiAgra, a source of humic acids, and cropped with Zea mays. The plant height, yield, and net calorific value of the aerial parts of maize, as well as its root yield, were determined. Additionally, the activity of seven soil enzymes and the values of the impact indices of compost and HumiAgra relative to the analyzed parameters were determined. It was found that Cr(VI) decreased the amount of energy obtained from the plants by decreasing maize biomass, and additionally by distorting the biochemical balance of the soil. Dehydrogenases, urease, and arylsulfatase proved to be particularly sensitive to this element. It was demonstrated that HumiAgra was more effective than compost in mollifying the adverse effects of Cr(VI) on the activity of soil enzymes and, consequently, on the biomass of Zea mays.
Energy Performance and Control Strategy for Dynamic Façade with Perovskite PV Panels—Technical Analysis and Case Study
Authors: Ożadowicz Andrzej , Walczyk Gabriela
Published: April 2023

Effective implementation of renewable energy sources (RES) is one of the main challenges in regard to the organization of local energy microgrids with buildings. One of the solutions is the use of dynamic building façades with photovoltaic (PV) panels, in particular the innovative perovskite solar cells (PSCs). This paper describes a case study performed on a pilot installation of perovskite PV panels located in Poland, Central-Eastern Europe. Results of preliminary measurements on this installation are provided in terms of verifying its energy efficiency and the possibility of selecting settings for the façade dynamics control system. Our experiments have considered the sun-tracking mechanism and its energy consumption as well as the impact of weather conditions at different times of the year. The energy efficiency results for the PV system, with average levels below 10%, are rather low. Therefore, even small energy savings in the operation of the PV system itself are significant. Changes in control scenarios for sun-tracking have been proposed and have obtained a reduction from 5% to 1% of energy consumption in autumn and from almost 3.2% to 0.6% in spring, in relation to overall energy produced by the PV system. The need for further experimental research from the perspective of the development and extension of the analyzed installation is pointed out as well.
Time-Inconsistent Bargaining and Cross-Commitments
Authors: Utset Manuel A.
Published: April 2023

The paper studies bargaining games involving players with present-biased preferences. The paper shows that the relative timing of bargaining rewards and bargaining costs will determine whether the players’ present-bias will affect bargaining outcomes. In cases where players agree to a bargain in period 1 and experience all bargaining payoffs in period 2, the players will act in a time-consistent fashion. When time-inconsistent players incur immediate bargaining costs to produce delayed rewards, they will have an incentive to procrastinate. On the other hand, when players receive immediate bargaining rewards and incur delayed costs, they will have incentives to agree to bargains too soon and to agree to inefficient bargains. The paper shows that the players’ awareness of their own and the other player’s present-biased preferences will determine whether they engage in repeated time-inconsistent bargaining. A naïve player who engages in time-inconsistent bargaining will suffer welfare losses. We show that time-inconsistent bargaining can also create spillover welfare losses for other players. A time-consistent player who is counterparty-naïve about the other player can suffer spillover welfare losses that can be higher than those incurred by the time-inconsistent player. As a result, counterparty-sophisticated players will have an incentive to use cross-commitment devices to reduce the likelihood of spillover welfare losses. The paper also shows that cross commitment devices that target immediate payoffs dominate cross-commitments that target delayed payoffs. Finally, the paper shows that time-inconsistent bargaining can lead to inefficient delays in agreeing to bargains and in exiting bargaining relationships.
Social Connectedness and Smoking among Adolescents in Ireland: An Analysis of the Health Behaviour in Schoolchildren Study
Authors: Evans David S. , O’Farrell Anne , Sheridan Aishling , Kavanagh Paul
Published: April 2023

Continuing progress with preventing smoking initiation is a key to the tobacco endgame. Home- and school-based social networks shape the health behaviour of children and adolescents. This study described the relationship between social connectedness and smoking behaviour in school-aged children in Ireland. The 2014 Irish Health Behaviour in School-aged Children (HBSC) surveyed self-reported smoking status and measured perceptions of social connectedness and support with validated and reliable questions across a random stratified sample of 9623 schoolchildren (aged 10–19). Overall, 8% of school-aged children reported smoking, in the last 30 days 52% reported smoking daily, and prevalence increased with age (p < 0.001). Compared with schoolchildren who did not smoke, perceptions of social connectedness and perceptions of support at home, from peers, and at school were significantly poorer for schoolchildren who smoked across all measures examined (p < 0.001). The poorest rated measures were for school connectedness and teacher support for smokers. Policies and practices that build and support positive environments for schoolchildren must continue to be prioritised if progress on preventing smoking initiation is to be sustained.
Management, Survival, and Costs of Pancreatic Cancer: Population-Based Observational Study in Catalonia
Authors: Guarga Laura , Paco Noelia , Manchon-Walsh Paula , Vela Emili , Delgadillo Joaquim , Pontes Caridad , Borràs Josep Maria
Published: April 2023

Aim: Few published studies comprehensively describe the characteristics of patients with pancreatic cancer and their treatment in clinical practice. This study aimed to describe the current clinical practice for treating pancreatic cancer in Catalonia, along with the associated survival and treatment costs. Methods: A retrospective observational cohort study in patients diagnosed with pancreatic cancer from 2014 to 2018, using data from the healthcare records of the Public Health System of Catalonia, was conducted. Treatment patterns and costs were described by age groups from 2014 to 2018, with survival reported until December 2021. Results: The proportion of patients receiving surgery with curative intent was low, especially in older patients (23% of patients <60 years and 9% of patients ≥80 years). The percentage of patients treated with drugs for unresectable disease also decreased with age (45% of patients <60 years and 8% of patients ≥80 years). Although age was associated with significant differences in survival after curative surgery, no differences attributable to age were observed in patients who received pharmacological treatment for unresectable disease. In patients under 60 years of age, the mean cost of the first year of treatment was EUR 17,730 (standard deviation [SD] 5754) in those receiving surgery and EUR 5398 (SD 9581) in those on pharmacological treatment for unresectable disease. In patients over 80, the mean costs were EUR 15,339 (SD 2634) and EUR 1845 (SD 3413), respectively. Conclusions: Half of the patients diagnosed with pancreatic cancer did not receive specific treatment. Surgery with curative intent was associated with longer survival, but only 18% of (mostly younger) patients received this treatment. Chemotherapy was also used less frequently in patients of advanced age, though survival in treated patients was comparable across all age groups, so careful oncogeriatric assessment is advisable to ensure the most appropriate indication for eligibility in older patients. In general, earlier diagnosis and more effective pharmacological treatments are necessary to treat frail patients with high comorbidity, a common profile in older patients.
Telemedicine among Adults Living in America during the COVID-19 Pandemic
Authors: Hung Man , Ocampo Monica , Raymond Benjamin , Mohajeri Amir , Lipsky Martin S.
Published: April 2023

Background and Objectives Telemedicine can expand healthcare access to populations, but relying on technology risks a digital divide. Therefore, it is important to understand who utilizes telemedicine. This study explores telemedicine usage across socio-demographic groups in the United States during COVID-19. Methods Data came from the Household Pulse Survey (HPS) between 14 April 2021, to 11 April 2022. HPS is a rapid online response survey that assesses household experiences during COVID-19. We calculated descriptive statistics and used cross-correlation to test each pair of the time series curves. Results High school graduates used the least telemedicine (20.58%), while those with some college (23.29%) or college graduates (22.61%) had similar levels, and those with less than a high school education fluctuated over time. Black people had higher levels of use (26.31%) than Asians (22.01%). Individuals with disabilities (35.40%) used telemedicine more than individuals without disabilities (20.21%). Individuals 80 years or over (27.63%) used telemedicine more than individuals 18 to 29 years old (18.44%). Cross-correlations for the time series pairs across demographics revealed significant differences in telemedicine use for all demographic groups over time. Conclusions Overall, elderly, Black people, individuals with some college, and persons with disabilities report higher levels of telemedicine use. Telemedicine may improve healthcare access post-pandemic, but more research is needed to understand factors that drive differences among groups.
Health Professionals’ Chronotype Association with Salivary Cortisol and Occupational Stress in Neonatal Intensive Care Units
Authors: de Azevedo Bringel Jocélia Maria , Abreu Isabel , Muniz Maria-Cláudia Mendes Caminha , de Almeida Paulo César , Silva Maria-Raquel G.
Published: April 2023

Burnout syndrome has been reported among health workers, particularly those working in critical areas, and is considered a significant public health problem. This study aimed to investigate the relationship between chronotype and work-related stress, as measured by salivary cortisol levels and burnout, among health professionals working in neonatal intensive care units. A cross-sectional study was conducted across four public hospitals in Fortaleza, Ceará, Brazil. Two hundred and fifty-six health professionals were administered the brazilian version of the Burnout Characterization Scale, the morningness–eveningness questionnaire, for chronotype, a sociodemographic questionnaire that included lifestyle habits and a salivary cortisol test. The results indicated that morning chronotype workers were significantly associated with the following: advanced age (p < 0.001), female gender (p = 0.032), married status (p = 0.014), and having children (p = 0.030) compared to those with evening and intermediate chronotypes. However, no significant association was found between signs of burnout syndrome and chronotype (p = 0.316). Participants whose work shift did not match their chronotype had significantly higher initial salivary cortisol levels (p = 0.013). The findings suggest that adapting working hours to an individual’s biological rhythm can help mitigate potential negative effects on physical and mental health. Thus, it is recommended that professionals’ working hours be adjusted accordingly.
STEP IN: Supporting Together Exercise and Play and Improving Nutrition; a Feasibility Study of Parent-Led Group Sessions and Fitness Trackers to Improve Family Healthy Lifestyle Behaviors in a Low-Income, Predominantly Black Population
Authors: Gorecki Michelle C. , Piotrowski Megan E. , Brown Courtney M. , Teli Radhika R. , Percy Zana , Lane Laura , Bolling Christopher F. , Siegel Robert M. , Copeland Kristen A.
Published: April 2023

Background: Pediatric obesity is prevalent and challenging to treat. Although family-centered behavioral management is the gold standard, many families face structural inequities to its access and efficacy. Identifying ways to manage pediatric obesity within primary care is needed. Methods: This feasibility study included three sequential trials of peer-led group sessions occurring biweekly or monthly between 3/2016 and 2/2017. Parent–child dyads were recruited from a large academic primary care clinic via mailed invitations, prioritizing patients living in local zip codes of historical disinvestment. Eligible patients were 6 to 12 years with a body mass index ≥85th percentile, with parent and child interest in making healthy lifestyle changes, and English speaking. Results: 27 dyads participated, 77% were non-Hispanic Black. Retention and attendance rates were highest in the initial four-session biweekly pilot (100%, 0 dropouts), high in the full six-session biweekly cohort (83%, 1 dropout), and moderate in the monthly cohort (62.7%, 4 dropouts). Families reported high satisfaction with the sessions (4.75/5). Qualitative comments suggested social connections had motivated behavior change in some families. Conclusion: Parent-led group sessions for pediatric weight management show promise in engaging families. A future large trial is needed to assess behavior change and anthropometric outcomes.
The Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma
Authors: Monjaras-Avila Cesar U. , Lorenzo-Leal Ana C. , Luque-Badillo Ana C. , D’Costa Ninadh , Chavez-Muñoz Claudia , Bach Horacio
Published: April 2023

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. Among these cells, CD8+ T cells are particularly important in controlling tumor growth by recognizing and killing cancer cells. However, the TIME of ccRCC is also characterized by an immunosuppressive environment that hinders the function of immune cells. Several mechanisms contribute to the immunosuppressive nature of the ccRCC TIME. For instance, ccRCC cells produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), which suppress immune cell activation and promote the differentiation of regulatory T cells (Tregs). Tregs, in turn, dampen the activity of effector T cells and promote tumor growth. In addition, ccRCC cells can express programmed death-ligand 1 (PD-L1), which interacts with the programmed cell death protein 1 (PD-1) receptor on T cells to inhibit their function. In addition, other immune checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3), also contribute to the immunosuppressive milieu of the ccRCC TIME. Finally, the hypoxic and nutrient-poor microenvironment of ccRCC can stimulate the production of immunosuppressive metabolites, such as adenosine and kynurenine, which further impair the function of immune cells. Understanding the complex interplay between tumor cells and the immune system in the ccRCC TIME is crucial for developing effective immunotherapies to treat this disease.
Immune Dysfunction in Medication-Related Osteonecrosis of the Jaw
Authors: Roato Ilaria , Mauceri Rodolfo , Notaro Vincenzo , Genova Tullio , Fusco Vittorio , Mussano Federico
Published: April 2023

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) is multifactorial and there is a substantial consensus on the role of antiresorptive drugs (ARDs), including bisphosphonates (BPs) and denosumab (Dmab), as one of the main determinants. The time exposure, cumulative dose and administration intensity of these drugs are critical parameters to be considered in the treatment of patients, as cancer patients show the highest incidence of MRONJ. BPs and Dmab have distinct mechanisms of action on bone, but they also exert different effects on immune subsets which interact with bone cells, thus contributing to the onset of MRONJ. Here, we summarized the main effects of ARDs on the different immune cell subsets, which consequently affect bone cells, particularly osteoclasts and osteoblasts. Data from animal models and MRONJ patients showed a deep interference of ARDs in modulating immune cells, even though a large part of the literature concerns the effects of BPs and there is a lack of data on Dmab, demonstrating the need to further studies.
Inhibition of DNA Repair Enzymes as a Valuable Pharmaceutical Approach
Authors: Volcho Konstantin P. , Lavrik Olga I.
Published: April 2023

The DNA repair system plays a crucial role in maintaining the integrity of the genome [...]
The Functional Role and Regulatory Mechanism of FTO m6A RNA Demethylase in Human Uterine Leiomyosarcoma
Authors: Yang Qiwei , Al-Hendy Ayman
Published: April 2023

Uterine leiomyosarcoma (uLMS) is the most frequent subtype of uterine sarcoma that presents a poor prognosis and high rates of recurrence and metastasis. The origin and molecular mechanism underlying and driving its clinical and biological behavior remain largely unknown. Recently, we and others have revealed the role of microRNAs, DNA methylation, and histone modifications in contributing to the pathogenesis of uLMS. However, the connection between reversible m6A RNA methylation and uLMS pathogenesis remains unclear. In this study, we assessed the role and mechanism of FTO m6A RNA demethylase in the pathogenesis of uLMS. Immunohistochemistry analysis revealed that the levels of RNA demethylases FTO and ALKBH5 were aberrantly upregulated in uLMS tissues compared to adjacent myometrium with a significant change by histochemical scoring assessment (p < 0.01). Furthermore, the inhibition of FTO demethylase with its small, potent inhibitor (Dac51) significantly decreased the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-seq analysis revealed that the inhibition of FTO with Dac51 exhibited a significant decrease in cell-cycle-related genes, including several CDK members, and a significant increase in the expression of CDKN1A, which correlated with a Dac51-exerted inhibitory effect on cell proliferation. Moreover, Dac51 treatment allowed the rewiring of several critical pathways, including TNFα signaling, KRAS signaling, inflammation response, G2M checkpoint, and C-Myc signaling, among others, leading to the suppression of the uLMS phenotype. Moreover, transcription factor (TF) analyses suggested that epitranscriptional alterations by Dac51 may alter the cell cycle-related gene expression via TF-driven pathways and epigenetic networks in uLMS cells. This intersection of RNA methylation and other epigenetic controls and pathways provides a framework to better understand uterine diseases, particularly uLMS pathogenesis with a dysregulation of RNA methylation machinery. Therefore, targeting the vulnerable epitranscriptome may provide an additional regulatory layer for a promising and novel strategy for treating patients with this aggressive uterine cancer.
In Vivo Efficacy and Toxicity of an Antimicrobial Peptide in a Model of Endotoxin-Induced Pulmonary Inflammation
Authors: Cresti Laura , Cappello Giovanni , Vailati Silvia , Melloni Elsa , Brunetti Jlenia , Falciani Chiara , Bracci Luisa , Pini Alessandro
Published: April 2023

SET-M33 is a synthetic peptide that is being developed as a new antibiotic against major Gram-negative bacteria. Here we report two in vivo studies to assess the toxicity and efficacy of the peptide in a murine model of pulmonary inflammation. First, we present the toxicity study in which SET-M33 was administered to CD-1 mice by snout inhalation exposure for 1 h/day for 7 days at doses of 5 and 20 mg/kg/day. The results showed adverse clinical signs and effects on body weight at the higher dose, as well as some treatment-related histopathology findings (lungs and bronchi, nose/turbinates, larynx and tracheal bifurcation). On this basis, the no observable adverse effect level (NOAEL) was considered to be 5 mg/kg/day. We then report an efficacy study of the peptide in an endotoxin (LPS)-induced pulmonary inflammation model. Intratracheal administration of SET-M33 at 0.5, 2 and 5 mg/kg significantly inhibited BAL neutrophil cell counts after an LPS challenge. A significant reduction in pro-inflammatory cytokines, KC, MIP-1α, IP-10, MCP-1 and TNF-α was also recorded after SET-M33 administration.
An Exploratory Study Using Next-Generation Sequencing to Identify Prothrombotic Variants in Patients with Cerebral Vein Thrombosis
Authors: Kramer Robert Anton , Zimmermann Robert , Strobel Julian , Achenbach Susanne , Ströbel Armin Michael , Hackstein Holger , Messerer David Alexander Christian , Schneider Sabine
Published: April 2023

Prothrombotic hereditary risk factors for cerebral vein thrombosis (CVT) are of clinical interest to better understand the underlying pathophysiology and stratify patients for the risk of recurrence. This study explores prothrombotic risk factors in CVT patients. An initial screening in patients of the outpatient clinic of the Department of Transfusion Medicine and Hemostaseology of the University Hospital Erlangen, Germany, revealed 183 patients with a history of CVT. An initial screening identified a number of common prothrombic risk factors, including Factor V Leiden (rs6025) and Prothrombin G20210A (rs1799963). All patients without relevant findings (58 individuals) were invited to participate in a subsequent genetic analysis of 55 relevant genes using next-generation sequencing (NGS). Three intron variants (ADAMTS13: rs28446901, FN1: rs56380797, rs35343655) were identified to occur with a significantly higher frequency in the CVT patient cohort compared to the general European population. Furthermore, the combined prevalence of at least two of four potentially prothrombic variants (FGA (rs6050), F13A1 (rs5985), ITGB3 (rs5918), and PROCR (rs867186)) was significantly higher in the CVT subjects. The possible impact of the identified variants on CVT is discussed.
Polyphenols and Triterpenes Combination in an In Vitro Model of Cardiac Damage: Protective Effects
Authors: de las Heras Natalia , Galiana Adrián , Ballesteros Sandra , Quintela José , Bonilauri Ileana , Lahera Vicente , Martín-Fernández Beatriz
Published: April 2023

Olive products contain high levels of monounsaturated fatty acids as well as other minor components such as triterpenic alcohols and other pentacyclic triterpenes, which together form the main triterpenes of virgin olive oil. Olive fruits and leaves contain significant amounts of hydrophilic and lipophilic bioactives including flavones, phenolic acids and phenolic alcohols, amongst others. Several studies have shown the benefits of these substances on the cardiovascular system. Regardless, little is known about the specific combination of bioactive compounds in cardiovascular health. Thus, we aimed to test the combination of a triterpenes (TT70) and a polyphenols (HT60) olive oil bioactive extract in H9c2 cells under stress conditions: LPS and H2O2 stimulation. To evaluate the effectiveness of the combination, we measured cell viability, superoxide production and protein expression of caspase 3, eNOS, peNOS, TNF-α and Il-6. Overall, cells stimulated with LPS or H2O2 and co-incubated with the combination of triterpenes and polyphenols had increased cell survival, lower levels of superoxide anion, lower protein expression of eNOS and higher expression of peNOS, increased protein expression of SOD-1 and lower protein expression of TNF-α and Il-6. The specific combination of HT60+TT70 is of great interest for further study as a possible treatment for cardiovascular damage.
Cross-Kingdom Regulation of Plant-Derived miRNAs in Modulating Insect Development
Authors: Chi Xuepeng , Wang Zhe , Wang Ying , Liu Zhenguo , Wang Hongfang , Xu Baohua
Published: April 2023

MicroRNAs (miRNAs), a class of non-coding small RNAs, are crucial regulatory factors in plants and animals at the post-transcriptional level. These tiny molecules suppress gene expression by complementary oligonucleotide binding to sites in the target messenger. Recently, the discovery of plant-derived miRNAs with cross-kingdom abilities to regulate gene expression in insects has promoted exciting discussion, although some controversies exist regarding the modulation of insect development by plant-derived miRNAs. Here, we review current knowledge about the mechanisms of miRNA biogenesis, the roles of miRNAs in coevolution between insects and plants, the regulation of insect development by plant-derived miRNAs, the cross-kingdom transport mechanisms of plant-derived miRNAs, and cross-kingdom regulation. In addition, the controversy regarding the modulation of insect development by plant-derived miRNAs also was discussed. Our review provides new insights for understanding complex plant–insect interactions and discovering new strategies for pest management and even crop genetic improvement.
Biological and Oxidative Degradation of Ultrathin-Fibrous Nonwovens Based on Poly(lactic Acid)/Poly(3-Hydroxybutyrate) Blends
Authors: Olkhov Anatoly Aleksandrovich , Mastalygina Elena Evgenyevna , Ovchinnikov Vasily Andreevich , Kurnosov Alexander Sergeevich , Popov Anatoly Anatolyevich , Iordanskii Alexey Leonidovich
Published: April 2023

Developing biodegradable materials based on polymer blends with a programmable self-destruction period in the environmental conditions of living systems is a promising direction in polymer chemistry. In this work, novel non-woven fibrous materials obtained by electrospinning based on the blends of poly(lactic acid) (PLA) and poly(3-hydroxybutyrate) (PHB) were developed. The kinetics of biodegradation was studied in the aquatic environment of the inoculum of soil microorganisms. Oxidative degradation was studied under the ozone gaseous medium. The changes in chemical composition and structure of the materials were studied by optical microscopy, DSC, TGA, and FTIR-spectroscopy. The disappearance of the structural bands of PHB in the IR-spectra of the blends and a significant decrease in the enthalpy of melting after 90 days of exposure in the inoculum indicated the biodegradation of PHB while PLA remained stable. It was shown that the rate of ozonation was higher for PLA and the blends with a high content of PLA. The lower density of the amorphous regions of the blends determined an increased rate of their oxidation by ozone compared to homopolymers. The optimal composition in terms of degradation kinetics is a fibrous material based on the blend of 30PLA/70PHB that can be used as an effective ecosorbent, for biopackaging, and as a highly porous covering material for agricultural purposes.
Mitochondrial Dysfunction, Altered Mitochondrial Oxygen, and Energy Metabolism Associated with the Pathogenesis of Schizophrenia
Authors: Fizíková Iveta , Dragašek Jozef , Račay Peter
Published: April 2023

The significant complexity of the brain can lead to the development of serious neuropsychiatric disorders, including schizophrenia. A number of mechanisms are involved in the etiopathogenesis of schizophrenia, pointing to its complexity and opening a new perspective on studying this disorder. In this review of currently published studies, we focused on the contribution of mitochondria to the process, with an emphasis on oxidative damage, ROS, and energy metabolism. In addition, we point out the influence of redox imbalance, which can lead to the occurrence of oxidative stress with increased lipid peroxidation, linked to the formation of toxic aldehydes such as 4-hydroxynonenal (4-HNE) and HNE protein adducts. We also analysed the role of lactate in the process of energy metabolism and cognitive functions in schizophrenia.
Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia
Authors: Nguyen Minh Tuan , Guseva Elizaveta V. , Ataeva Aida N. , Sigan Andrey L. , Shibaeva Anna V. , Dmitrieva Maria V. , Burtsev Ivan D. , Volodina Yulia L. , Radchenko Alexandra S. , Egorov Anton E. , Kostyukov Alexey A. , Melnikov Pavel V. , Chkanikov Nikolai D. , Kuzmin Vladimir A. , Shtil Alexander A. , Markova Alina A.
Published: April 2023

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells.
Defective Induction of IL-27-Mediated Immunoregulation by Myeloid DCs in Multiple Sclerosis
Authors: von Glehn Felipe , Pochet Nathalie , Thapa Bibek , Raheja Radhika , Mazzola Maria A. , Jangi Sushrut , Beynon Vanessa , Huang Junning , Farias Alessandro S. , Paul Anu , Santos Leonilda M. B. , Gandhi Roopali , Murugaiyan Gopal , Weiner Howard L. , Baecher-Allan Clare M.
Published: April 2023

The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 ± lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion. mDCs isolated from HCs but not untreated MS patients became functionally tolerogenic after IL-27 treatment. Although IL-27 induced both HC and untreated MS mDCs to produce similar amounts of IL-10, the tolerogenic HC mDCs expressed PD-L2, IDO1, and SOCS1, while the non-tolerogenic untreated MS mDCs expressed IDO1 and IL-6R. Cytokine and RNA analyses identified two signature blocks: the first identified genes associated with mDC tolerizing responses to IL-27, while the second was associated with the presence of MS. In contrast to mDCs from untreated MS patients, mDCs from HCs and IFNb-treated MS patients became tolerogenic in response to IL-27. The genes differentially expressed in the different donor IL-27-treated mDCs may contain targets that regulate mDC tolerogenic responses.