bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the IGF2 Methylation Score in Diagnosing Adrenocortical Tumors with Unclear Malignant Potential—Feasibility of Formalin-Fixed Paraffin-Embedded Tissue
Authors: Steenaard Rebecca V. , Feelders Richard A. , Dogan Fadime , van Koetsveld Peter M. , Creemers Sara G. , Ettaieb Madeleine H. T. , van Kemenade Folkert J. , Haak Harm R. , Hofland Leo J.
Published: July 2023

The differentiation between benign and malignant adrenocortical tumors based on pathological assessment can be difficult. We present a series of 17 patients with unclear malignant tumors, of whom six had recurrent or metastatic disease. The assessment of the methylation pattern of insulin-like growth factor 2 (IGF2) regulatory regions in fresh frozen material has shown to be valuable in determining the malignancy of adrenocortical tumors, although this has not been elaborately tested in unclear malignant tumors. Since fresh frozen tissue was only available in six of the patients, we determined the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue for this method. We isolated DNA from FFPE tissue and matched the fresh frozen tissue of three patients with adrenocortical carcinoma. Methylation patterns of IGF2 regulatory regions were determined by pyrosequencing using different amounts of bisulfite-converted DNA (5 ng, 20 ng, 40 ng). Compared to fresh frozen tissue, FFPE tissue had a higher failure rate (fresh frozen 0%; FFPE 18.5%) and poor-to-moderate replicability (fresh frozen rho = 0.89–0.99, median variation 1.6%; FFPE rho = −0.09–0.85, median variation 7.7%). There was only a poor-to-moderate correlation between results from fresh frozen and FFPE tissue (rho = −0.28–0.70, median variation 13.2%). In conclusion, FFPE tissue is not suitable for determining the IGF2 methylation score in patients with an unclear malignant adrenocortical tumor using the currently used method. We, therefore, recommend fresh frozen storage of resection material for diagnostic and biobank purposes.
Impact of Western Diet and Ultra-Processed Food on the Intestinal Mucus Barrier
Authors: Stolfi Carmine , Pacifico Teresa , Monteleone Giovanni , Laudisi Federica
Published: July 2023

The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further protection due to mucin secretion and maturation by goblet cells, thus representing a crucial player in maintaining intestinal homeostasis. However, environmental factors, such as dietary products, can disrupt this equilibrium, leading to the development of inflammatory intestinal disorders. In particular, ultra-processed food, which is broadly present in the Western diet and includes dietary components containing food additives and/or undergoing multiple industrial processes (such as dry heating cooking), was shown to negatively impact intestinal health. In this review, we summarize and discuss current knowledge on the impact of a Western diet and, in particular, ultra-processed food on the mucus barrier and goblet cell function, as well as potential therapeutic approaches to maintain and restore the mucus layer under pathological conditions.
Preservation of Mechanical and Morphological Properties of Porcine Cardiac Outflow Vessels after Decellularization and Wet Storage
Authors: Sergeevichev David , Vasiliyeva Maria , Kuznetsova Elena , Chelobanov Boris
Published: July 2023

Widely used storage methods, including freezing or chemical modification, preserve the sterility of biological tissues but degrade the mechanical properties of materials used to make heart valve prostheses. Therefore, wet storage remains the most optimal option for biomaterials. Three biocidal solutions (an antibiotic mixture, an octanediol-phenoxyethanol complex solution, and a glycerol-ethanol mixture) were studied for the storage of native and decellularized porcine aorta and pulmonary trunk. Subsequent mechanical testing and microstructural analysis showed a slight increase in the tensile strength of native and decellularized aorta in the longitudinal direction. Pulmonary trunk elongation increased 1.3–1.6 times in the longitudinal direction after decellularization only. The microstructures of the tested specimens showed no differences before and after wet storage. Thus, two months of wet storage of native and decellularized porcine aorta and pulmonary trunks does not significantly affect the strength and elastic properties of the material. The wet storage protocol using alcohol solutions of glycerol or octanediol-phenoxyethanol mixture may be intended for further fabrication of extracellular matrix for tissue-engineered biological heart valve prostheses.
Conventional Imaging, MRI and 18F-FDG PET/MRI for N and M Staging in Patients with Newly Diagnosed Breast Cancer
Authors: Morawitz Janna , Bruckmann Nils-Martin , Jannusch Kai , Dietzel Frederic , Milosevic Aleksandar , Bittner Ann-Kathrin , Hoffmann Oliver , Mohrmann Svjetlana , Ruckhäberle Eugen , Häberle Lena , Fendler Wolfgang Peter , Herrmann Ken , Giesel Frederik Lars , Antoch Gerald , Umutlu Lale , Kowall Bernd , Stang Andreas , Kirchner Julian
Published: July 2023

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18F-FDG PET/MRI. 18F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI (p < 0.0001 and p = 0.0005). Furthermore, 18F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions:18F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.
Integrated Multi-Omic Analysis Reveals Immunosuppressive Phenotype Associated with Poor Outcomes in High-Grade Serous Ovarian Cancer
Authors: Keathley Russell , Kocherginsky Masha , Davuluri Ramana , Matei Daniela
Published: July 2023

High-grade serous ovarian cancer (HGSOC) is characterized by a complex genomic landscape, with both genetic and epigenetic diversity contributing to its pathogenesis, disease course, and response to treatment. To better understand the association between genomic features and response to treatment among 370 patients with newly diagnosed HGSOC, we utilized multi-omic data and semi-biased clustering of HGSOC specimens profiled by TCGA. A Cox regression model was deployed to select model input features based on the influence on disease recurrence. Among the features most significantly correlated with recurrence were the promotor-associated probes for the NFRKB and DPT genes and the TREML1 gene. Using 1467 transcriptomic and methylomic features as input to consensus clustering, we identified four distinct tumor clusters—three of which had noteworthy differences in treatment response and time to disease recurrence. Each cluster had unique divergence in differential analyses and distinctly enriched pathways therein. Differences in predicted stromal and immune cell-type composition were also observed, with an immune-suppressive phenotype specific to one cluster, which associated with short time to disease recurrence. Our model features were additionally used as a neural network input layer to validate the previously defined clusters with high prediction accuracy (91.3%). Overall, our approach highlights an integrated data utilization workflow from tumor-derived samples, which can be used to uncover novel drivers of clinical outcomes.
Disturbed Plasma Lipidomic Profiles in Females with Diffuse Large B-Cell Lymphoma: A Pilot Study
Authors: Masnikosa Romana , Pirić David , Post Julia Maria , Cvetković Zorica , Petrović Snježana , Paunović Marija , Vučić Vesna , Bindila Laura
Published: July 2023

Lipidome dysregulation is a hallmark of cancer and inflammation. The global plasma lipidome and sub-lipidome of inflammatory pathways have not been reported in diffuse large B-cell lymphoma (DLBCL). In a pilot study of plasma lipid variation in female DLBCL patients and BMI-matched disease-free controls, we performed targeted lipidomics using LC-MRM to quantify lipid mediators of inflammation and immunity, and those known or hypothesised to be involved in cancer progression: sphingolipids, resolvin D1, arachidonic acid (AA)-derived oxylipins, such as hydroxyeicosatetraenoic acids (HETEs) and dihydroxyeicosatrienoic acids, along with their membrane structural precursors. We report on the role of the eicosanoids in the separation of DLBCL from controls, along with lysophosphatidylinositol LPI 20:4, implying notable changes in lipid metabolic and/or signalling pathways, particularly pertaining to AA lipoxygenase pathway and glycerophospholipid remodelling in the cell membrane. We suggest here the set of S1P, SM 36:1, SM 34:1 and PI 34:1 as DLBCL lipid signatures which could serve as a basis for the prospective validation in larger DLBCL cohorts. Additionally, untargeted lipidomics indicates a substantial change in the overall lipid metabolism in DLBCL. The plasma lipid profiling of DLBCL patients helps to better understand the specific lipid dysregulations and pathways in this cancer.
Modeling of Heat Flux in a Heating Furnace
Authors: Varga Augustín , Kizek Ján , Rimár Miroslav , Fedák Marcel , Čorný Ivan , Lukáč Ladislav
Published: July 2023

Modern heating furnaces use combined modes of heating the charge. At high heating temperatures, more radiation heating is used; at lower temperatures, more convection heating is used. In large heating furnaces, such as pusher furnaces, it is necessary to monitor the heating of the material zonally. Zonal heating allows the appropriate thermal regime to be set in each zone, according to the desired parameters for heating the charge. The problem for each heating furnace is to set the optimum thermal regime so that at the end of the heating, after the material has been cross-sectioned, there is a uniform temperature field with a minimum temperature differential. In order to evaluate the heating of the charge, a mathematical model was developed to calculate the heat fluxes of the moving charge (slabs) along the length of the pusher furnace. The obtained results are based on experimental measurements on a test slab on which thermocouples were installed, and data acquisition was provided by a TERMOPHIL-stor data logger placed directly on the slab. Most of the developed models focus only on energy balance assessment or external heat exchange. The results from the model created showed reserves for changing the thermal regimes in the different zones. The developed model was used to compare the heating evaluation of the slabs after the rebuilding of the pusher furnace. Changing the furnace parameters and altering the heat fluxes or heating regimes in each zone contributed to more uniform heating and a reduction in specific heat consumption. The developed mathematical heat flux model is applicable as part of the powerful tools for monitoring and controlling the thermal condition of the charge inside the furnace as well as evaluating the operating condition of such furnaces.
Young’s Experiment with Entangled Bipartite Systems: The Role of Underlying Quantum Velocity Fields
Authors: Sanz Ángel S.
Published: July 2023

We consider the concept of velocity fields, taken from Bohmian mechanics, to investigate the dynamical effects of entanglement in bipartite realizations of Young’s two-slit experiment. In particular, by comparing the behavior exhibited by factorizable two-slit states (cat-type state analogs in the position representation) with the dynamics exhibited by a continuous-variable Bell-type maximally entangled state, we find that, while the velocity fields associated with each particle in the separable scenario are well-defined and act separately on each subspace, in the entangled case there is a strong deformation in the total space that prevents this behavior. Consequently, the trajectories for each subsystem are not constrained any longer to remain confined within the corresponding subspace; rather, they exhibit seemingly wandering behavior across the total space. In this way, within the subspace associated with each particle (that is, when we trace over the other subsystem), not only interference features are washed out, but also the so-called Bohmian non-crossing rule (i.e., particle trajectories are allowed to get across the same point at the same time).
Exploring the Macroeconomic Drivers of International Bilateral Remittance Flows: A Gravity-Model Approach
Authors: Fagiolo Giorgio , Rughi Tommaso
Published: July 2023

This paper investigates the macroeconomic determinants of global bilateral remittance flows. Unlike existing studies, which have been often hampered by the lack of comprehensive and large-enough datasets, we use data originally covering 214 countries over the 2010–2017 period. We employ a gravity-model approach to explore the role played by dyadic and country-specific covariates in explaining remittances. We find that remittance flows are robustly and strongly impacted by size effects (i.e., number of migrants in the host country and population at home), transaction costs, common social, political, and cultural ties, output growth rate, and financial development at home. We also document the existence of a robust non-linear relationship between per capita income at home and remittance flows, both in the aggregate and across income groups.
Low-Temperature Sinterable Cu@Ag Paste with Superior Strength Driven by Pre-Heating Process
Authors: Won Miso , Kim Dajung , Yang Hyunseung , Oh Chulmin
Published: July 2023

To preserve the structural integrity of power semiconductor devices, ensuring a reliable connection between wide-bandgap (WBG) chips and their substrates at temperatures above 200 °C is crucial. Therefore, easily processable chip-attach materials with high bonding strengths at high temperatures should be developed. Herein, we determined the optimal pre-heating conditions of chip-attach materials to achieve highly reliable WBG semiconductor devices. Sintering with silver-coated copper (Cu@Ag) particle paste was investigated as a model system for chip attachment in electric power devices. After printing the paste onto a direct-bonded ceramic substrate and placing the Si chip on the paste, the pre-heating process was conducted at 50 and 70 °C for different periods of time. Finally, the samples were sintered at a pressure of 9 MPa at 250 °C in an N2 atmosphere for 1 h. The quality of the obtained Cu@Ag joints significantly varied depending on the pre-heating temperature and time. When Cu@Ag joints were pre-heated at 50 °C, more reliable and reproducible bonding was achieved than at 70 °C. In particular, high-quality sintered joints were obtained with a pre-heating time of 4 min. However, after excessive pre-heating time, cracks and voids were generated impacting negatively the performance of the sintered joints.
Numerical Modeling of the Micromechanics Damage of an Offshore Electrical High-Voltage Phase
Authors: Ech-Cheikh Fouad , Drissi-Habti Monssef
Published: July 2023

Due to the strong growth of offshore renewable energies, research and engineering in this field is constantly expanding. One of the centerpieces of these technologies is the high-voltage electrical cable, generally made of copper, to transport the energy produced from the offshore farm to the onshore station. The critical nature of these cables lies in the proven resistance that they must demonstrate during stays underwater for several years, even decades, in difficult environmental conditions, which begin at the handling, shipping and underground burial stage. The marine environment can lead to deformation of the copper wires well beyond the limit of proportionality and, consequently, to breakage. Copper, although being an exceptional electrical conductor, has very poor mechanical properties. The plasticity generated by the excessive deformation of copper wires affects all of the physical properties of copper. When plasticity develops, electrical transport is affected and the heat within copper increases, but care should be given to not exceed 90 °C, as this would result in the shutdown of the cable with dramatic economic consequences. The work carried out in this article, which is part of the National Project EMODI as well as the European Project FLOW-CAM, aims at studying the mechanical behavior of the phase in order to correlate the deformation levels reached to the phase geometry as well as operating mechanisms of damage which reflect the proliferation of microstructural defects within the conductor. To do this, we propose a numerical model using Abaqus. Correct description of the effects of several parameters (geometry of the phase) and plasticity development on the performance of the phase were simulated and discussed.
Review on the Optimal Configuration of Distributed Energy Storage
Authors: Liu Ziqi , Su Tingting , Quan Zhiying , Wu Quanli , Wang Yu
Published: July 2023

With the large-scale access of renewable energy, the randomness, fluctuation and intermittency of renewable energy have great influence on the stable operation of a power system. Energy storage is considered to be an important flexible resource to enhance the flexibility of the power grid, absorb a high proportion of new energy and satisfy the dynamic balance between the supply and demand of a system. At present, the cost of energy storage is still high, and how to achieve the optimal energy storage configuration is the primary problem to be solved. Therefore, the current research progress in energy storage application scenarios, modeling method and optimal configuration strategies on the power generation side, grid side and user side are summarized in this paper. On this basis, the shortcomings that still exist of energy storage configuration research are summarized, and the future research direction for energy storage configuration is prospected. This review can provide reference for the latest development and future research and innovation direction for energy storage configuration.
Planning and Operation Objectives of Public Electric Vehicle Charging Infrastructures: A Review
Authors: Anadón Martínez Verónica , Sumper Andreas
Published: July 2023

Planning public electric vehicle (EV) charging infrastructure has gradually become a key factor in the electrification of mobility and decarbonization of the transport sector. In order to achieve a high level of electrification in mobility, in recent years, different studies have been presented, proposing novel practices and methodologies for the planning and operation of electric vehicles charging infrastructure. In this paper, the authors present an up-to-date analysis of the existing literature in this research field, organized by considering the perspectives and objectives of the principal actors/operators of the EV public charging infrastructure value chain. Among these actors, the electric vehicle, the charging operators and service providers, and the power system infrastructure (transmission and distribution system) are analyzed in depth. By classifying the reviewed literature based on this manifold viewpoints approach, this paper aims to facilitate researchers and technology developers in exploring the state-of-the-art methodologies for each actor’s perspective, and identify conflicting interests and synergies in charging infrastructure operation and planning.
Experimental Investigation of Coupled Transport Mechanisms in a PEM Based Thermoelectric Energy Converter
Authors: Willke Maike , Rahm Nils-Eric , Kabelac Stephan
Published: July 2023

Thermoelectric energy converters based on galvanic cells (TGC) offer the possibility of direct conversion of low-temperature waste heat into electrical energy and could therefore be a promising approach for an increase in the overall efficiency of energy conversion. Due to an externally applied heat source, a temperature gradient across the electrolyte is induced, leading to a gradient in the chemical potential of the species and an electrical potential difference between the electrodes. The aim of approaching an internal equilibrium state leads to various coupled molecular transport mechanisms taking place in the electrolyte, impacting the open circuit voltage (OCV) and the performance of the TGC. By applying the theory of non-equilibrium thermodynamics (NET) to describe these coupled processes, the interactions that occur can be characterized in more detail. In this work, a polymer electrolyte membrane (PEM)-based TGC with two H2/H2O electrodes of different temperatures and gas compositions is experimentally investigated. By controlling the gradients in temperature and concentration, different impacts on the resulting OCV can be identified. In addition, we present the measured coupling coefficient, representing the singular relation between the transport of the hydrogen ions inside the membrane and the electrical potential difference between the electrodes for a wide variety of working conditions.
Parametric Optimization of Ferrite Structure Used for Dynamic Wireless Power Transfer for 3 kW Electric Vehicle
Authors: Bensetti Mohamed , Kadem Karim , Pei Yao , Le Bihan Yann , Labouré Eric , Pichon Lionel
Published: July 2023

The current charging technology for electric vehicles consists of plugging the cable from the AC utility to charge the batteries. This requires heavy gauge cables to connect to electric vehicles, which can be difficult to handle, presents tripping hazards, and is prone to vandalism. In addition to these inconveniences, electric vehicles must be immobilized for hours before being fully charged. Dynamic wireless power transfer has been studied worldwide as a promising technology. It is safe and convenient and allows electric vehicles to charge while moving. To improve the efficiency of a dynamic wireless power transfer system, the magnetic coupling coefficient must be maximized between the primary pad, which is integrated into the road, and the secondary pad installed in the electric vehicle. This article presents a parametric optimization of the ferrite structure used for a 3 kW dynamic wireless power transfer prototype. Different ferrite configurations are compared while studying the effect of the parameter values on their magnetic coupling coefficient. Finally, the proposed structure was validated during the experimental test, and its coupling coefficient was improved by 26% compared to the original structure.
The Role of Bedrock Geochemistry and Climate in Soil Organic Matter Stability in Subtropical Karst Forests of Southwest China
Authors: Tang Tiangang , Hu Peilei , Zhang Wei , Xiao Dan , Tang Li , Xiao Jun , Zhao Jie , Wang Kelin
Published: July 2023

The stability of soil organic matter (SOM) plays a critical role in soil carbon (C) dynamics under global warming. However, the factors influencing SOM stability, particularly the significance of bedrock geochemistry and its hierarchical relationship with climate and soil properties, remain poorly understood. To address this gap, we conducted a study along a large climatic gradient (Δtemperature > 9 °C) in the subtropical karst forests of southwest China, quantifying SOM stability using thermal analysis and investigating the contributions of bedrock geochemistry, climate, and soil properties. Our results showed that SOM stability was positively correlated with mineral-associated organic C (MAOC) rather than particulate organic C. Hierarchical partitioning analysis further demonstrated that bedrock geochemistry was the predominant contributor to SOM stability variance, accounting for 23.7%. Following this, soil minerals contributed to 21.1%–22.6% of the variance, the mean annual temperature to 20.3%, and microbial biomass C to 17.2%. In particular, bedrock geochemistry—specifically the presence of calcium-rich bedrock—was found to enhance SOM stability by promoting the accumulation of exchangeable calcium and calcium carbonate in soils. Additionally, high temperature improved SOM stability by increasing the content and proportion of MAOC and soil pH. These results highlight the fundamental role of bedrock geochemistry in controlling SOM stability and emphasize the importance of considering hierarchical relationships among bedrock–soil–climate interactions for evaluating soil C dynamics.
Progressive Cone-Rod Dystrophy and RPE Dysfunction in Mitfmi/+ Mice
Authors: García-Llorca Andrea , Ólafsson Knútur Haukstein , Sigurdsson Arnór Thorri , Eysteinsson Thor
Published: July 2023

Mutations in the mouse microphthalmia-associated transcription factor (Mitf) gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to hypopigmentation, microphthalmia, deafness, and blindness. For instance, an association has been established between loss-of-function mutations in the mouse Mitf gene and a variety of human retinal diseases, including Waardenburg type 2 and Tietz syndromes. Although there is evidence showing that mice with the homozygous Mitfmi mutation manifest microphthalmia and osteopetrosis, there are limited or no data on the effects of the heterozygous condition in the eye. Mitf mice can therefore be regarded as an important model system for the study of human disease. Thus, we characterized Mitfmi/+ mice at 1, 3, 12, and 18 months old in comparison with age-matched wild-type mice. The light- and dark-adapted electroretinogram (ERG) recordings showed progressive cone-rod dystrophy in Mitfmi/+ mice. The RPE response was reduced in the mutant in all age groups studied. Progressive loss of pigmentation was found in Mitfmi/+ mice. Histological retinal sections revealed evidence of retinal degeneration in Mitfmi/+ mice at older ages. For the first time, we report a mouse model of progressive cone-rod dystrophy and RPE dysfunction with a mutation in the Mitf gene.
Association of Single Nucleotide Polymorphisms of Cytokine Genes with Depression, Schizophrenia and Bipolar Disorder
Authors: Mikhalitskaya Ekaterina V. , Vyalova Natalya M. , Ermakov Evgeny A. , Levchuk Lyudmila A. , Simutkin German G. , Bokhan Nikolay A. , Ivanova Svetlana A.
Published: July 2023

Immune gene variants are known to be associated with the risk of psychiatric disorders, their clinical manifestations, and their response to therapy. This narrative review summarizes the current literature over the past decade on the association of polymorphic variants of cytokine genes with risk, severity, and response to treatment for severe mental disorders such as bipolar disorder, depression, and schizophrenia. A search of literature in databases was carried out using keywords related to depressive disorder, bipolar disorder, schizophrenia, inflammation, and cytokines. Gene lists were extracted from publications to identify common genes and pathways for these mental disorders. Associations between polymorphic variants of the IL1B, IL6, and TNFA genes were the most replicated and relevant in depression. Polymorphic variants of the IL1B, IL6, IL6R, IL10, IL17A, and TNFA genes have been associated with schizophrenia. Bipolar disorder has mainly been associated with polymorphic variants of the IL1B gene. Interestingly, the IL6R gene polymorphism (rs2228145) was associated with all three diseases. Some cytokine genes have also been associated with clinical presentation and response to pharmacotherapy. There is also evidence that some specific polymorphic variants may affect the expression of cytokine genes. Thus, the data from this review indicate a link between neuroinflammation and severe mental disorders.
Acupuncture Improves Sleep Disorders and Depression among Patients with Parkinson’s Disease: A Meta-Analysis
Authors: Hsu Wei-Ti , Hsu Chieh-Min , Hung Shao-Chi , Hung Shih-Ya
Published: July 2023

Parkinson’s disease (PD) is associated with a range of non-motor symptoms that lack effective treatments. Acupuncture is a popular alternative therapy for PD patients that has been shown to improve motor symptoms. However, the efficacy of acupuncture in treating non-motor symptoms has remained controversial. The goal of our study was to systematically assess the existing evidence for acupuncture’s efficacy in treating PD non-motor symptoms of sleep disorders, depression, anxiety, and fatigue. We conducted a meta-analysis of clinical trials by searching Pubmed, Embase, CINAHL, and Web of Science as electronic databases to evaluate acupuncture treatment for PD non-motor symptoms. Thirteen clinical trials met our inclusion criteria, and their methodological quality was assessed using the modified Jadad scale, indicating a moderate overall quality. Our results showed that acupuncture improved PD-related sleep disorders and depression but had no effect on anxiety and fatigue. Our meta-analysis suggests that acupuncture can be used as a complementary treatment for sleep disturbances and depression in PD patients and may exhibit a dual therapeutic effect on motor and non-motor symptoms. However, further well-designed clinical trials with larger sample sizes are needed to confirm these findings. Overall, our study highlights the potential of acupuncture as a viable complementary therapy for the treatment of PD non-motor symptoms of sleep disorders and depression, which can improve the quality of life of PD patients.
Identifying the Drivers of Inter-Regional Patients’ Mobility: An Analysis on Hospital Beds Endowment
Authors: Guarducci Giovanni , Messina Gabriele , Carbone Simona , Nante Nicola
Published: July 2023

Background: In a Beveridgean decentralized healthcare system, like the Italian one, where regions are responsible for their own health planning and financing, the analysis of patients’ mobility appears very interesting as it has economic and social implications. The study aims to analyze both patients’ mobility for hospital rehabilitation and if the beds endowment is a driver for these flows; Methods: From 2011 to 2019, admissions data were collected from the Hospital Discharge Cards database of the Italian Ministry of Health, population data from the Italian National Institute of Statistics and data on beds endowment from the Italian Ministry of Health website. To evaluate patients’ mobility, we used Gandy’s Nomogram, while to assess if beds endowments are mobility drivers, we created two matrices, one with attraction indexes (AI) and one with escape indexes (EI). The beds endowment, for each Italian region, was correlated with AI and EI. Spearman’s test was carried out through STATA software; Results: Gandy’s Nomogram showed that only some northern regions had good hospital planning for rehabilitation. A statistically significant correlation between beds endowment and AI was found for four regions and with EI for eight regions; Conclusions: Only some northern regions appear able to satisfy the care needs of their residents, with a positive attractions minus escapes epidemiological balance. The beds endowment seems to be a driver of patients’ mobility, mainly for escapes. Certainly, the search for mobility drivers needs further investigation given the situation in Molise and Basilicata.
Description of Two Promising Walnut (Juglans regia L.) Selections with Lateral Bud Fruitfulness and Large Nuts
Authors: Manthos Ioannis , Rouskas Dimos , Sotiropoulos Thomas , Botu Mihai
Published: July 2023

Walnut (Juglans regia) populations are considered a valuable genetic resource for genetic variability conservation and walnut cultivar improvement. In the current study, two walnut selections from Central Greece, “FM3” and “FM6”, were evaluated for their characteristics to determine their perspective as new cultivars. Their main phenological and pomological characteristics were assessed according to IPGR (1994) and UPOV-TG/125/6 (1999) criteria for 10 consecutive years and compared with “Chandler”. Results revealed that “FM3” presents high lateral flowering (70–80%), whereas “FM6” is 30–35%. Although the date of bud break and male blooming of both selections did not differ from “Chandler” (p > 0.05), the female blooming phase of “FM6” occurred earlier (p < 0.05) than “Chandler” and nut harvest was earlier than both “Chandler” and “FM3” (p < 0.05). Nut dimensions of both selections were higher than “Chandler” (p < 0.001). The mean in-shell nut weight and kernel weight of “FM3” were higher than “FM6” and “Chandler”, and those of “FM6” were higher than “Chandler” (p < 0.001). Other positive nut characteristics were their light kernel color, the well kernel fill, and the easy removal of the kernel halves. Thus, the current results indicate that “FM3” and “FM6” could be considered promising gene pools in crossbreeding activities.
Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2
Authors: Amankwa Charles E. , Young Olivia , DebNath Biddut , Gondi Sudershan R. , Rangan Rajiv , Ellis Dorette Z. , Zode Gulab , Stankowska Dorota L. , Acharya Suchismita
Published: July 2023

Oxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates for the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and antioxidant activity reduced intraocular pressure and improved aqueous humor outflow in rodent eyes. Here, we examined the mechanistic role of SA-2 in trabecular meshwork (TM) cells in vitro and measured the activity of intracellular antioxidant enzymes during OS. Primary human TM cells isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors and transformed glaucomatous TM cells (GTM-3) were used for in vitro assays. We examined the effect of SA-2 on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro using Seahorse Analyzer with or without the oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations of total antioxidant enzymes, catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. We observed significant protection of both hNTM and hGTM cells from TBHP-induced cell death by SA-2. Antioxidant enzymes were elevated in SA-2-treated cells compared to TBHP-treated cells. In addition, SA-2 demonstrated an increase in mitochondrial metabolic parameters. Altogether, SA-2 protected both normal and glaucomatous TM cells from OS via increasing mitochondrial energy parameters and the activity of antioxidant enzymes.
Advances in the Biosynthesis of Terpenoids and Their Ecological Functions in Plant Resistance
Authors: Li Changyan , Zha Wenjun , Li Wei , Wang Jianyu , You Aiqing
Published: July 2023

Secondary metabolism plays an important role in the adaptation of plants to their environments, particularly by mediating bio-interactions and protecting plants from herbivores, insects, and pathogens. Terpenoids form the largest group of plant secondary metabolites, and their biosynthesis and regulation are extremely complicated. Terpenoids are key players in the interactions and defense reactions between plants, microorganisms, and animals. Terpene compounds are of great significance both to plants themselves and the ecological environment. On the one hand, while protecting plants themselves, they can also have an impact on the environment, thereby affecting the evolution of plant communities and even ecosystems. On the other hand, their economic value is gradually becoming clear in various aspects of human life; their potential is enormous, and they have broad application prospects. Therefore, research on terpenoids is crucial for plants, especially crops. This review paper is mainly focused on the following six aspects: plant terpenes (especially terpene volatiles and plant defense); their ecological functions; their biosynthesis and transport; related synthesis genes and their regulation; terpene homologues; and research and application prospects. We will provide readers with a systematic introduction to terpenoids covering the above aspects.
Anti-Cancer Effect of Chlorophyllin-Assisted Photodynamic Therapy to Induce Apoptosis through Oxidative Stress on Human Cervical Cancer
Authors: Heo Seong-Yeong , Lee Yeachan , Kim Tae-Hee , Heo Soo-Jin , Shin Hwarang , Lee Jiho , Yi Myunggi , Kang Hyun Wook , Jung Won-Kyo
Published: July 2023

Photodynamic therapy is an alternative approach to treating tumors that utilizes photochemical reactions between a photosensitizer and laser irradiation for the generation of reactive oxygen species. Currently, natural photosensitive compounds are being promised to replace synthetic photosensitizers used in photodynamic therapy because of their low toxicity, lesser side effects, and high solubility in water. Therefore, the present study investigated the anti-cancer efficacy of chlorophyllin-assisted photodynamic therapy on human cervical cancer by inducing apoptotic response through oxidative stress. The chlorophyllin-assisted photodynamic therapy significantly induced cytotoxicity, and the optimal conditions were determined based on the results, including laser irradiation time, laser power density, and chlorophyllin concentration. In addition, reactive oxygen species generation and Annexin V expression level were detected on the photodynamic reaction-treated HeLa cells under the optimized conditions to evaluate apoptosis using a fluorescence microscope. In the Western blotting analysis, the photodynamic therapy group showed the increased protein expression level of the cleaved caspase 8, caspase 9, Bax, and cytochrome C, and the suppressed protein expression level of Bcl-2, pro-caspase 8, and pro-caspase 9. Moreover, the proposed photodynamic therapy downregulated the phosphorylation of AKT1 in the HeLa cells. Therefore, our results suggest that the chlorophyllin-assisted photodynamic therapy has potential as an antitumor therapy for cervical cancer.
Comparative Evaluation of the Repair Bond Strength of Dental Resin Composite after Sodium Bicarbonate or Aluminum Oxide Air-Abrasion
Authors: Németh Kinga Dorottya , Told Roland , Szabó Péter , Maróti Péter , Szénai Réka , Pintér Zsolt Balázs , Lovász Bálint Viktor , Szalma József , Lempel Edina
Published: July 2023

The dental prophylactic cleaning of a damaged resin-based composite (RBC) restoration with sodium bicarbonate can change the surface characteristics and influence the repair bond strength. The purpose of this study was to compare the effect of sodium bicarbonate (SB) and aluminum oxide (AO) surface treatments on the microtensile bond strength (µTBS) of repaired, aged RBC. Bar specimens were prepared from microhybrid RBC and aged in deionized water for 8 weeks. Different surface treatments (AO air-abrasion; SB air-polishing), as well as cleaning (phosphoric acid, PA; ethylene-diamine-tetraacetic-acid, EDTA) and adhesive applications (single bottle etch-and-rinse, ER; universal adhesive, UA), were used prior to the application of the repair RBC. Not aged and aged but not surface treated RBCs were used as positive and negative controls, respectively. The repaired blocks were cut into sticks using a precision grinding machine. The specimens were tested for tensile fracture and the µTBS values were calculated. Surface characteristics were assessed using scanning electron microscopy. AO-PA-UA (62.6 MPa) showed a 20% increase in µTBS compared to the NC (50.2 MPa), which proved to be the most significant. This was followed by SB-EDTA-UA (58.9 MPa) with an increase of 15%. In addition to AO-PA-UA, SB-EDTA-UA could also be a viable alternative in the RBC repair protocol.
Construction, Expression, and Evaluation of the Naturally Acquired Humoral Immune Response against Plasmodium vivax RMC-1, a Multistage Chimeric Protein
Authors: Matos Ada da Silva , Soares Isabela Ferreira , Baptista Barbara de Oliveira , de Souza Hugo Amorim dos Santos , Chaves Lana Bitencourt , Perce-da-Silva Daiana de Souza , Riccio Evelyn Kety Pratt , Albrecht Letusa , Totino Paulo Renato Rivas , Rodrigues-da-Silva Rodrigo Nunes , Daniel-Ribeiro Cláudio Tadeu , Pratt-Riccio Lilian Rose , Lima-Junior Josué da Costa
Published: July 2023

The PvCelTOS, PvCyRPA, and Pvs25 proteins play important roles during the three stages of the P. vivax lifecycle. In this study, we designed and expressed a P. vivax recombinant modular chimeric protein (PvRMC-1) composed of the main antigenic regions of these vaccine candidates. After structure modelling by prediction, the chimeric protein was expressed, and the antigenicity was assessed by IgM and IgG (total and subclass) ELISA in 301 naturally exposed individuals from the Brazilian Amazon. The recombinant protein was recognized by IgG (54%) and IgM (40%) antibodies in the studied individuals, confirming the natural immunogenicity of the epitopes that composed PvRMC-1 as its maintenance in the chimeric structure. Among responders, a predominant cytophilic response mediated by IgG1 (70%) and IgG3 (69%) was observed. IgM levels were inversely correlated with age and time of residence in endemic areas (p < 0.01). By contrast, the IgG and IgM reactivity indexes were positively correlated with each other, and both were inversely correlated with the time of the last malaria episode. Conclusions: The study demonstrates that PvRMC-1 was successfully expressed and targeted by natural antibodies, providing important insights into the construction of a multistage chimeric recombinant protein and the use of naturally acquired antibodies to validate the construction.
IHF and Fis as Escherichia coli Cell Cycle Regulators: Activation of the Replication Origin oriC and the Regulatory Cycle of the DnaA Initiator
Authors: Kasho Kazutoshi , Ozaki Shogo , Katayama Tsutomu
Published: July 2023

This review summarizes current knowledge about the mechanisms of timely binding and dissociation of two nucleoid proteins, IHF and Fis, which play fundamental roles in the initiation of chromosomal DNA replication in Escherichia coli. Replication is initiated from a unique replication origin called oriC and is tightly regulated so that it occurs only once per cell cycle. The timing of replication initiation at oriC is rigidly controlled by the timely binding of the initiator protein DnaA and IHF to oriC. The first part of this review presents up-to-date knowledge about the timely stabilization of oriC-IHF binding at oriC during replication initiation. Recent advances in our understanding of the genome-wide profile of cell cycle-coordinated IHF binding have revealed the oriC-specific stabilization of IHF binding by ATP-DnaA oligomers at oriC and by an initiation-specific IHF binding consensus sequence at oriC. The second part of this review summarizes the mechanism of the timely regulation of DnaA activity via the chromosomal loci DARS2 (DnaA-reactivating sequence 2) and datA. The timing of replication initiation at oriC is controlled predominantly by the phosphorylated form of the adenosine nucleotide bound to DnaA, i.e., ATP-DnaA, but not ADP-ADP, is competent for initiation. Before initiation, DARS2 increases the level of ATP-DnaA by stimulating the exchange of ADP for ATP on DnaA. This DARS2 function is activated by the site-specific and timely binding of both IHF and Fis within DARS2. After initiation, another chromosomal locus, datA, which inactivates ATP-DnaA by stimulating ATP hydrolysis, is activated by the timely binding of IHF. A recent study has shown that ATP-DnaA oligomers formed at DARS2-Fis binding sites competitively dissociate Fis via negative feedback, whereas IHF regulation at DARS2 and datA still remains to be investigated. This review summarizes the current knowledge about the specific role of IHF and Fis in the regulation of replication initiation and proposes a mechanism for the regulation of timely IHF binding and dissociation at DARS2 and datA.
Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization
Authors: Shibata Mamoru , Kitagawa Satoshi , Unekawa Miyuki , Takizawa Tsubasa , Nakahara Jin
Published: July 2023

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14–18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.