bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-Term Campus Load Forecasting Using CNN-Based Encoder–Decoder Network with Attention
Authors: Ahmed Zain , Jamil Mohsin , Khan Ashraf Ali
Published: September 2024

Short-term load forecasting is a challenging research problem and has a tremendous impact on electricity generation, transmission, and distribution. A robust forecasting algorithm can help power system operators to better tackle the ever-changing electric power demand. This paper presents a novel deep neural network for short-term electric load forecasting for the St. John’s campus of Memorial University of Newfoundland (MUN). The electric load data are obtained from the Memorial University of Newfoundland and combined with metrological data from St. John’s. This dataset is used to formulate a multivariate time-series forecasting problem. A novel deep learning algorithm is presented, consisting of a 1D Convolutional Neural Network, which is followed by an encoder–decoder-based network with attention. The input used for this model is the electric load consumption and metrological data, while the output is the hourly prediction of the next day. The model is compared with Gated Recurrent Unit (GRU) and Long Short Term Memory (LSTM)-based Recurrent Neural Network. A CNN-based encoder–decoder model without attention is also tested. The proposed model shows a lower mean absolute error (MAE), mean squared error (MSE), mean absolute percentage error (MAPE), and higher R2 score. These evaluation metrics show an improved performance compared to GRU and LSTM-based RNNs as well as the CNN encoder–decoder model without attention.
Enhanced Microgrid Control through Genetic Predictive Control: Integrating Genetic Algorithms with Model Predictive Control for Improved Non-Linearity and Non-Convexity Handling
Authors: Cavus Muhammed , Allahham Adib
Published: September 2024

Microgrid (MG) control is crucial for efficient, reliable, and sustainable energy management in distributed energy systems. Genetic Algorithm-based energy management systems (GA-EMS) can optimally control MGs by solving complex, non-linear, and non-convex problems but may struggle with real-time application due to their computational demands. Model Predictive Control (MPC)-based EMS, which predicts future behaviour to ensure optimal performance, usually depends on linear models. This paper introduces a novel Genetic Predictive Control (GPC) method that combines a GA and MPC to enhance resource allocation, balance multiple objectives, and adapt dynamically to changing conditions. Integrating GAs with MPC improves the handling of non-linearities and non-convexity, resulting in more accurate and effective control. Comparative analysis reveals that GPC significantly reduces excess power production, improves resource allocation, and balances cost, emissions, and power efficiency. For example, in the Mutation–Random Selection scenario, GPC reduced excess power to 76.0 W compared to 87.0 W with GA; in the Crossover-Elitism scenario, GPC achieved a lower daily cost of USD 113.94 versus the GA’s USD 127.80 and reduced carbon emissions to 52.83 kg CO2e compared to the GA’s 69.71 kg CO2e. While MPC optimises a weighted sum of objectives, setting appropriate weights can be difficult and may lead to non-convex problems. GAs offer multi-objective optimisation, providing Pareto-optimal solutions. GPC maintains optimal performance by forecasting future load demands and adjusting control actions dynamically. Although GPC can sometimes result in higher costs, such as USD 113.94 compared to USD 131.90 in the Crossover–Random Selection scenario, it achieves a better balance among various metrics, proving cost-effective in the long term. By reducing excess power and emissions, GPC promotes economic savings and sustainability. These findings highlight GPC’s potential as a versatile, efficient, and environmentally beneficial tool for power generation systems.
Are Strong Baselines Enough? False News Detection with Machine Learning
Authors: Aslan Lara , Ptaszynski Michal , Jauhiainen Jukka
Published: September 2024

False news refers to false, fake, or misleading information presented as real news. In recent years, there has been a noticeable increase in false news on the Internet. The goal of this paper was to study the automatic detection of such false news using machine learning and natural language processing techniques and to determine which techniques work the most effectively. This article first studies what constitutes false news and how it differs from other types of misleading information. We also study the results achieved by other researchers on the same topic. After building a foundation to understand false news and the various ways of automatically detecting it, this article provides its own experiments. These experiments were carried out on four different datasets, one that was made just for this article, using 10 different machine learning methods. The results of this article were satisfactory and provided answers to the original research questions set up at the beginning of this article. This article could determine from the experiments that passive aggressive algorithms, support vector machines, and random forests are the most efficient methods for automatic false news detection. This article also concluded that more complex experiments, such as using multiple levels of identifying false news or detecting computer-generated false news, require more complex machine learning models.
Evaluation of Bioactive Compounds and Antioxidant and Cytotoxic Effects of Oil and Pulp without Açaí Fat (Euterpe oleracea) Obtained by Supercritical Extraction
Authors: Siqueira Letícia Maria Martins , Campos Ana Luiza de Barros Souza , Pires Flávia Cristina Seabra , Ferreira Maria Caroline Rodrigues , Silva Ana Paula de Souza e , Menezes Eduardo Gama Ortiz , Ramos Ingryd Nayara de Farias , Khayat André Salim , Rêgo José de Arimateia Rodrigues do , Carvalho Junior Raul Nunes de
Published: September 2024

For bioactivity studies, it is necessary to use products with a high degree of purity, which may influence the cytotoxic effects. Supercritical technology presents itself as an alternative to obtain these products. Therefore, the objective of this work was to obtain the bioactive compounds of oil and pulp of açaí fat-free supercritical technology and evaluate the cytotoxicity of products in MRC-5 and VERO cells in vitro. The açaí pulp was subjected to extraction with supercritical CO2 to obtain the oil and pulp without fat, under conditions of 323.15 K at 35 MPa, 333.15 K at 42 MPa, and 343.15 K at 49 MPa. The largest yields (51.74%), carotenoids (277.09 µg/g), DPPH (2.55 μmol TE/g), ABTS (2.60 μmol TE/g), and FRAP (15.25 μm of SF/g) of oil and ABTS (644.23 μmol TE/g) of pulp without fat were found in the condition 343.15 K at 49 MPa. The highest levels of compounds phenolics (150.20 mg GAE/g), DPPH (414.99 μmol TE/g), and FRAP (746.2 μm SF/g) of the pulp without fat were found in the condition of 323.15 K to 35 MPa. The fat-free pulp presented high levels of anthocyanins without significant variation in cytotoxicity. The developed process was efficient in obtaining oil rich in carotenoids, and the supercritical technology elucidated an efficient way to obtain açaí fat-free pulp.
Investigating the Effect of High-Voltage Electrostatic Field (HVEF) Treatment on the Physicochemical Characteristics, Bioactive Substances Content, and Shelf Life of Tomatoes
Authors: Nie Xiaobao , Zuo Zhijie , Zhou Li , Gao Zhe , Cheng Lilin , Wang Xiaoli , Nie Linghong , Huang Ping-Hsiu
Published: September 2024

This study evaluated the ability of a high-voltage electrostatic field (HVEF) treatment to extend the shelf life of tomatoes. Tomatoes were exposed to HVEF treatment for different lengths of time, and the physicochemical properties of tomatoes and bioactive compounds were monitored during 28 days of storage at 4 °C. The results indicated that the quality parameters of tomatoes were better maintained during storage by the HVEF treatment relative to the control treatment, extending their shelf life by 14–28 days. The HVEF treatment mitigated losses in firmness, weight, color changes, and bioactive substances, such as total phenolic content, total flavonoid content, ascorbic acid, and lycopene. The activity of pectin-degrading enzymes was also inhibited. The best exposure times for the HVEF treatment were 90 and 120 min. While the measured parameters decreased in both the control and HVEF treatment groups, the decrease in all of these measured parameters was significantly less (p < 0.05) in the optimum HVEF treatment groups than in the control. While the physicochemical properties may vary between different tomato varieties, the HVEF treatment of harvested tomatoes for 90 or 120 min can mitigate the degradation of quality parameters and loss of bioactive compounds incurred during the postharvest storage of tomatoes, thus maintaining their commercial value.
Factors Affecting CPAP Adherence in an OSA Population during the First Two Years of the COVID-19 Pandemic
Authors: Lykouras Dimosthenis , Zarkadi Eirini , Koulousousa Electra , Lagiou Olga , Komninos Dimitrios , Tzouvelekis Argyris , Karkoulias Kyriakos
Published: September 2024

Background: Obstructive sleep apnea (OSA) is a common disorder associated with major cardiovascular and neurocognitive sequelae. Continuous positive airway pressure (CPAP) is the standard treatment for OSA. The aim of this study was to investigate the prevalence and associations of long-term CPAP adherence in newly diagnosed OSA patients. Methods: We enrolled patients who were diagnosed with OSA during the COVID-19 pandemic. Adherence was defined as CPAP use ≥4 h per night on ≥70% of nights over 30 consecutive days. Patient demographics were retrieved from medical records, and CPAP adherence at 6 months and 1 year after initiation was monitored. Results: Overall, 107 patients were included in the analysis. A number of 73 (68%) and 63 (59%) patients were adherent to CPAP treatment at 6 months and 12 months accordingly. Among the factors examined and analyzed (age, gender, BMI, Apnea–Hypopnea Index (AHI)), no significant correlation was found. Further analysis revealed the potential role of comorbidities. CPAP compliance at 6 months was shown to be associated with better CPAP adherence at 12 months. Conclusions: CPAP adherence at 6 months is correlated to long-term adherence to treatment. Therefore, early close follow-up is important. Further prospective studies are needed to identify other potential predictors.
Prevalence of Perinatal Depression and Its Associated Risk Factors among Nepalese Women in Kathmandu, Nepal
Authors: Wasti Pratikshya , Panta Prem Prasad , Gc Vijay S. , Ghimire Biwash , Sapkota Pooja , Wasti Sharada Prasad
Published: September 2024

Perinatal mental health is a major public health issue that arises during pregnancy and/or after birth, with substantial implications for social, parental, and maternal functioning, as well as overall quality of life. The study aimed to determine the prevalence of perinatal depression and its associated risk factors among women who visited a maternity hospital in Kathmandu, Nepal. A cross-sectional study was conducted at the Paropakar Maternity and Women’s Hospital in Kathmandu. A total of 300 women in their perinatal period were interviewed. The Edinburgh Perinatal Depression Scale (EPDS) was used to measure perinatal depression. The Poisson regression model was used to determine risk factors associated with perinatal depression. The mean age of respondents was 25.5 (SD 4.5) years; average age during their first pregnancy was 23.5 (SD 3.7) years; and 53.7% of respondents were in the antenatal period. The prevalence of depressive symptoms (EPDS ≥ 10) was 40% (95% CI 31.4% to 45.8%). Unsupportive family members (adjusted prevalence ratio [aPR] 2.23; 95% CI 1.75–2.86), postnatal period (aPR 2.64; 95% CI 1.97–3.53), complications faced during delivery (aPR 1.76; 95%CI 1.30–2.39), history of intimate partner violence (aPR 0.48; 95% CI 0.36–0.64), and first pregnancy at the age of ≤25 years (aPR 0.61; 95% CI 0.42–0.88) were identified as key risk factors of perinatal depression. Strong family support and the active involvement of partners in counselling can contribute to alleviating perinatal depression symptoms. Targeted interventions in health and well-being services should be implemented to address mental health burden during both pregnancy and postpartum periods.
Managing Surgical Risks in Hemophilic Elbow Arthropathy: An In-Depth Case Study and Literature Review
Authors: Pasta Gianluigi , Annunziata Salvatore , Ruggieri Roberta , Abruzzi Dario , Arrigoni Paolo , Jannelli Eugenio , Benazzo Francesco , Pedrotti Luisella , Viola Erika Maria , Rodriguez-Merchan Emérito Carlos , Mosconi Mario
Published: September 2024

This study presents a detailed case analysis of a 40-year-old male patient with hemophilia A and severe chronic elbow arthropathy, exploring the surgical challenges and outcomes within the context of the current literature. The patient, with a history of multiple comorbidities including Hodgkin’s lymphoma and cardiomyopathy, exhibited significant joint damage and functional impairment. A comprehensive approach was employed, collecting all relevant clinical data, including radiographic and MRI findings, to inform treatment decisions. Clinical findings and treatment decisions are presented as they occurred in real time, simulating the clinical reasoning process. Subsequent references to the clinical and instrumental findings as well therapeutic interventions are discussed in light of the current literature to reinforce the decision-making framework. This report underscores the importance of multidisciplinary care in optimizing patient outcomes and contributes to the ongoing discourse on the management of advanced musculoskeletal conditions in hemophilic patients. The findings emphasize the necessity for early intervention and specialized care to mitigate complications and improve long-term prognosis.
Temporary Immersion Culture: A Potential In Vitro Culture Method for the Clonal Propagation of Coconut
Authors: Mu Zhihua , Li Zhiying , Bazrafshan Amirhossein , Kalaipandian Sundaravelpandian , Kong Eveline Yee Yan , Biddle Julianne , Nulu Naga Prafulla Chandrika , Adkins Steve
Published: September 2024

As one of the most important members of the palm family, coconut (Cocos nucifera L.) currently faces a substantial gap between demand and production. Current plantings of this crop are aging, and these traditional varieties are susceptible to several devastating pests and diseases. Consequently, there is an urgent need to replant and expand coconut lands with new, genetically superior varieties. Such replanting cannot be met through the conventional method of seed nut planting, and tissue culture has emerged as a likely solution to address this problem. However, due to certain technical barriers, elevated costs, and a need for improved efficiency, the development of automated and highly efficient tissue culture techniques is yet to be developed. The present research explores the potential of an in vitro temporary immersion system (TIS) to improve the production of somatic embryogenic callus for plantlet regeneration. Results indicated that, in comparison to the conventional agar-based method used to produce coconut somatic embryogenic callus, the TIS method significantly enhanced embryogenic callus production. The optimal biomass of callus for inoculating the TIS was determined to be 0.2 g in each 900 mL vessel and the most favorable embryogenic developmental stage for employing TIS was the globular stage of embryo development. The most effective immersion time to give the highest yield of embryogenic callus was 5 min every 6 h. This foundational research demonstrates that a TIS step is likely to be important to rapidly produce, on a large scale, coconut plantlets to meet the escalating demand for materials for the replanting of coconut lands.
Nutrient Deficiency-Induced Stress Improves Skincare Effects and Phytochemical Content of Green Extracts from Lamiaceae In Vitro Cultures
Authors: Mansinhos Inês , Gonçalves Sandra , Rodríguez-Solana Raquel , Pereira-Caro Gema , Moreno-Rojas José , Romano Anabela
Published: September 2024

The objective of this study was to investigate the impact of nutrient starvation on the growth, biochemical, metabolomic, and biological traits of Lavandula viridis L’Hér and Thymus lotocephalus G. López and R. Morales in vitro cultures. In both species, a reduction in shoot growth and in the production of chlorophyll and carotenoids was observed in cultures grown under nutrient-deficient media (especially Fe and N) compared to those grown under control conditions. The highest levels of hydrogen peroxide and lipid peroxidation, two indicators of oxidative stress, were observed in L. viridis cultures grown under N deficiency and in T. lotocephalus under P and Fe limitation. The results demonstrated that nutrient deficiency led to a 72% and 62% increase in the quantified phenolic compounds in L. viridis and T. lotocephalus, respectively. The highest concentrations of the major compound in both species—rosmarinic acid—were observed in cultures grown under Mg-deficient (60.7 ± 1.0 mg/gDW) and Fe-deficient (50.0 ± 0.4 mg/gDW) conditions in L. viridis and T. lotocephalus, respectively. Furthermore, nutrient starvation enhanced the capacity of green extracts to inhibit three enzymes (tyrosinase, elastase, and hyaluronidase) associated with anti-aging and their antioxidant properties.
Fruit Position on Tree Canopy Affects Fruit Quality Traits in ‘Sanguinelli’ Blood Oranges
Authors: Serna-Escolano Vicente , Giménez María , Serrano María , Valero Daniel , García-Pastor María , Dobón-Suarez Alicia , Gutiérrez-Pozo María , Giménez-Berenguer Marina , Zapata Pedro
Published: September 2024

In modern orchard systems, the tree canopy is designed to ensure homogeneity in fruit quality. However, even in those crops there are some variables that affect the fruit maturation process and fruit quality properties. The aim of this work was to determine if canopy layer (upper vs. lower), fruit shoot position (grouped vs. individual) and orientation (west vs. east) affect fruit quality attributes of ‘Sanguinelli’ blood oranges. Thus, different quality traits, such as weight, internal colour (IC), external colour (EC), total soluble solids (TSS), titratable acidity (TA) and maturity index (MI) were determined for this purpose. Results showed that fruit weight, internal colour, TA and MI were influenced by the number of fruits per shoot. In this sense, the highest values of weight, IC and MI were found in the grouped fruits, while the highest values in TA were in the individual fruits. Regarding the EC and TSS, they were strongly related to the canopy layer, since the highest values were found in fruit located at the upper parts of the canopy. On the contrary, the orientation did not have a significant effect on fruit quality properties. Therefore, consistent differences in quality traits of ‘Sanguinelli’ blood oranges fruits were observed depending on canopy layer and number of fruits per shoot.
Racial Attitudes and Perceptions of Government Response during the COVID-19 Pandemic: Implications for Public Health Strategies
Authors: Hung Man , Franklin Jeremy D. , Smith William A. , Crespo Carlos J. , Ezikwelu Evelyn U. , Bounsanga Jerry , Lipsky Martin S.
Published: September 2024

Background: This study explored whether opinions about the government’s role in addressing the COVID-19 pandemic vary based on demographic characteristics and racial beliefs. We hypothesized that opinions about the United States (U.S.) government’s response to COVID-19 would differ based on an individual’s characteristics such as age, race, and racial beliefs. Methods: We utilized an Inter-University Consortium for Political and Social Research dataset to examine differences in opinion regarding the government’s pandemic response, considering personal characteristics and racial beliefs. Descriptive statistics depicted respondents’ characteristics, and a Chi-square test for independence assessed whether differences emerged based on racial attitude, self-reported racial identity, sex, income, education, and age. Logistic regression analyses were conducted to independently determine which characteristics were associated with differences in evaluating the government’s pandemic response. Results: The sample consisted of 1028 respondents: 47.5% male and 52.5% female. Overall, the group viewed the government unfavorably, with only 40% reporting that the government responded correctly and 54% believing the government is almost always wasteful and inefficient. Hispanics or Latinos were more likely to view the government as wasteful or inefficient, while more Whites rated the government’s pandemic response as appropriate. Individuals who believed that racial discrimination is the main reason why many Black people cannot get ahead generally regarded the government’s pandemic response more favorably. Only 5% deemed the government’s response excessive. Being Black, younger, and female was associated with the view that racial discrimination is the main reason why many Black people cannot get ahead. Individuals who felt this way viewed the government unfavorably by almost a 2:1 ratio. Conclusions: A majority of U.S. residents do not believe the government responded correctly to the pandemic and more than half viewed the government as wasteful and inefficient. Differences emerged by ethnicity and racial attitudes, with individuals of color holding more negative views of the government’s response. Understanding this perspective can help develop messaging and strategies that resonate with communities where racial and minority groups live.
Characterizing the Role of Geospatial Science in Digital Twins
Authors: Metcalfe Jack , Ellul Claire , Morley Jeremy , Stoter Jantien
Published: September 2024

Delivering value from digital concepts such as Digital Twins is necessary to address systemic national and global issues, such as achieving Net Zero. However, there is still a lack of consensus over what a Digital Twin (DT) is and efforts to clarify this do not consider the Geospatial perspective. With the aspiration for national- and international-scale DTs, it is important that the Geospatial community understands its role in supporting the realisation of the value of these DTs. Here, a systematic literature review is used to gather DT case studies that use, or are inferred to use, elements of the Geospatial discipline. A total of 77 DT case studies about smart cities, manufacturing, energy, construction and agriculture are reviewed in full, and 24 Geospatial DT dimensions are defined and then compared with existing DT dimensions. The results indicate a considerable use of Geospatial Science in DTs that is not explicitly stated, meaning that there are possibly missed opportunities for collaboration between the Geospatial and DT communities. We conclude that the role of Geospatial Science in DTs is larger than stated and needs to be understood further.
Investigating the Anti-Inflammatory, Analgesic, and Chondroprotective Effects of Gynostemma pentaphyllum (Thunb.) Makino in Osteoarthritis: An In Vitro and In Vivo Study
Authors: Jo Hee-Geun , Baek Chae Yun , Hwang Yeseul , Baek Eunhye , Park Chanyoon , Song Ho Sueb , Lee Donghun
Published: September 2024

Osteoarthritis (OA) is an age-related disease characterized by inflammation, pain, articular cartilage damage, synovitis, and irreversible disability. Gynostemma pentaphyllum (Thunb.) Makino (GP), a herbal medicine traditionally used in East Asia for its anti-inflammatory properties, was investigated for its potential to modulate OA pathology and symptoms. This study evaluated GP’s efficacy in inhibiting pain, functional decline, and cartilage destruction in monosodium iodoacetate-induced OA and acetic acid-induced writhing models. Additionally, the effects of GP on OA-related inflammatory targets were assessed via mRNA and protein expression in rat knee cartilage and lipopolysaccharide-induced RAW 264.7 cells. The GP group demonstrated significant pain relief, functional improvement, and cartilage protection. Notably, GP inhibited key inflammatory mediators, including interleukin (IL)-1β, IL-6, matrix metalloproteinases (MMP)-3 and MMP-13, cyclooxygenase-2, and prostaglandin E receptor 2, surpassing the effects of active controls. These findings suggest that GP is a promising candidate for disease-modifying OA drugs and warrants further comprehensive studies.
A Spironolactone-Based Prototype of an Innovative Biomedical Patch for Wound Dressing Applications
Authors: Aquino Giovanna , Viscusi Gianluca , D’Alterio Massimo Christian , Covelli Verdiana , Gorrasi Giuliana , Pellecchia Claudio , Rizzo Paola , D’Ursi Anna Maria , Pepe Giacomo , Amante Chiara , Del Gaudio Pasquale , Rodriquez Manuela
Published: September 2024

The electrospinning process is an effective technique for creating micro- and nanofibers from synthetic and natural polymers, with significant potential for biomedical applications and drug delivery systems due to their high drug-loading capacity, large surface area, and tunable release times. Poly(L-lactic acid) (PLLA) stands out for its excellent thermo-mechanical properties, biodegradability, and bioabsorbability. Electrospun PLLA nanofibrous structures have been extensively investigated as wound dressings, sutures, drug delivery carriers, and tissue engineering scaffolds. This study aims to create and characterize electrospun PLLA membranes loaded with spironolactone (SP), mimicking active compounds of Ganoderma lucidum (GL), to develop a biodegradable patch for topical wound-healing applications. GL, a medicinal mushroom, enhances dermal wound healing with its bioactive compounds, such as polysaccharides and ganoderic acids. Focusing on GL extracts—obtained through green extraction methods—and innovative drug delivery, we created new fibers for wound-healing potential applications. To integrate complex mixtures of bioactive compounds into the fibers, we developed a prototype using a single pure substance representing the extract mixture. This painstaking work presents the results of the fabricating, wetting, moisture properties, material resilience, and full characterization of the product, providing a robust rationale for the fabrication of fibers imbued with more complex extracts.
UTRs and Ago-2/miR-335 Complex Restricts Amylin Translation in Insulinoma and Human Pancreatic β-Cells
Authors: Kudaibergenova Zhanar , Pany Satyabrata , Placheril Elizabeth , Jeremic Aleksandar M.
Published: September 2024

Amylin promoter and transcriptional factors are well-established, inducible factors in the production of the main amyloidogenic pancreatic hormone, human islet amyloid peptide (hIAPP) or amylin. However, posttranscriptional mechanisms driving hIAPP expression in pancreas remain enigmatic, and hence were explored here. The translational assay revealed that both 5′ and 3′ untranslated regions (UTRs) of hIAPP restricted expression of the luciferase constructs only in constructs driven by the hIAPP promoter. Bioinformatics analysis revealed several putative seed sequences for a dozen micro RNAs (miRNAs) in hIAPP’s 3′ UTR. miR-182, miR-335, and miR-495 were the most downregulated miRNAs in stressed human islets exposed to endoplasmic reticulum (ER) or metabolic stressors, thapsigargin (TG) or high glucose (HG). Correspondingly, miR-335 mimics alone or in combination with miR-495 and miR-182 mimics significantly and potently (>3-fold) reduced hIAPP protein expression in HG-treated cultured human islets. siRNA-mediated silencing of Ago2 but not Ago1 significantly stimulated hIAPP expression and secretion from transfected, HG-treated human islets. Conversely, ectopic expression of Ago2 in hIAPP-expressing RIN-m5F cell line driven by CMV promoter reduced hIAPP intracellular protein levels. Collectively, the results point to a novel and synergistic role for hIAPP promoter, 5/3′ UTRs and Ago-2/miR-335 complex in post-transcriptional regulation of hIAPP gene expression in normal and metabolically active β-cells.
The Impact of a Non-Pathogenic Strain of Fusarium Oxysporum on Structural and Biochemical Properties of Flax Suspension Cultures
Authors: Wróbel-Kwiatkowska Magdalena , Osika Aleksandra , Liszka Justyna , Lipiński Mateusz , Dymińska Lucyna , Piegza Michał , Rymowicz Waldemar
Published: September 2024

Flax (Linum usitatissimum L.) is an important crop plant with pharmaceutical significance. It is described in pharmacopoeias (the United States Pharmacopeia and the European Pharmacopoeia), which confirms that it (especially the seeds) is a valuable medicinal product. Similar to flax seeds, which accumulate bioactive compounds, flax in vitro cultures are also a rich source of flavonoids, phenolics, lignans and neolignans. In the present study, flax suspension cultures after treatment of the non-pathogenic Fusarium oxysporum strain Fo47 were established and analyzed. The study examined the suitability of Fo47 as an elicitor in flax suspension cultures and provided interesting data on the impact of these endophytic fungi on plant metabolism and physiology. Two flax cultivars (Bukoz and Nike) and two compositions of media for flax callus liquid cultures were tested. Biochemical analysis revealed enhanced levels of secondary metabolites (total flavonoid and total phenolic content) and photosynthetically active pigments in the flax callus cultures after treatment with the non-pathogenic fungal strain F. oxysporum Fo47 when compared to control, untreated cultures. In cultures with the selected, optimized conditions, FTIR analysis was performed and revealed changes in the structural properties of cell wall polymers after elicitation of cultures with F. oxysporum Fo47. The plant cell wall polymers were more strongly bound, and the crystallinity index (Icr) of cellulose was higher than in control, untreated samples. However, lignin and pectin levels were lower in the flax callus liquid cultures treated with the non-pathogenic strain of Fusarium when compared to the untreated control. The potential application of the non-pathogenic strain of F. oxysporum for enhancing the synthesis of desired secondary metabolites in plant tissue cultures is discussed.
Ccn2 Deletion Reduces Cardiac Dysfunction, Oxidative Markers, and Fibrosis Induced by Doxorubicin Administration in Mice
Authors: Tejera-Muñoz Antonio , Cortés Marcelino , Rodriguez-Rodriguez Alianet , Tejedor-Santamaria Lucia , Marchant Vanessa , Rayego-Mateos Sandra , Gimeno-Longas Maria José , Leask Andrew , Nguyen Tri Q. , Martín María , Tuñón Jose , Rodríguez Isabel , Ruiz-Ortega Marta , Rodrigues-Díez Raul R.
Published: September 2024

Cellular Communication Network Factor 2 (CCN2) is a matricellular protein implicated in cell communication and microenvironmental signaling. Overexpression of CCN2 has been documented in various cardiovascular pathologies, wherein it may exert either deleterious or protective effects depending on the pathological context, thereby suggesting that its role in the cardiovascular system is not yet fully elucidated. In this study, we aimed to investigate the effects of Ccn2 gene deletion on the progression of acute cardiac injury induced by doxorubicin (DOX), a widely utilized chemotherapeutic agent. To this end, we employed conditional knockout (KO) mice for the Ccn2 gene (CCN2-KO), which were administered DOX and compared to DOX-treated wild-type (WT) control mice. Our findings demonstrated that the ablation of CCN2 ameliorated DOX-induced cardiac dysfunction, as evidenced by improvements in ejection fraction (EF) and fractional shortening (FS) of the left ventricle. Furthermore, DOX-treated CCN2-KO mice exhibited a significant reduction in the gene expression and activation of oxidative stress markers (Hmox1 and Nfe2l2/NRF2) relative to DOX-treated WT controls. Additionally, the deletion of Ccn2 markedly attenuated DOX-induced cardiac fibrosis. Collectively, these results suggest that CCN2 plays a pivotal role in the pathogenesis of DOX-mediated cardiotoxicity by modulating oxidative stress and fibrotic pathways. These findings provide a novel avenue for future investigations to explore the therapeutic potential of targeting CCN2 in the prevention of DOX-induced cardiac dysfunction.
Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis
Authors: Kim So-Yeon , Lee Sookyoung , Park Jong-Tae , Lee Su-Jin , Kim Hyung-Seok
Published: September 2024

Exosomes are nanovesicles 30–150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.
Complement-Mediated Two-Step NETosis: Serum-Induced Complement Activation and Calcium Influx Generate NADPH Oxidase-Dependent NETs in Serum-Free Conditions
Authors: Maqsood Maria , Suntharalingham Samuel , Khan Meraj , Ortiz-Sandoval Carolina G. , Feitz Wouter J. C. , Palaniyar Nades , Licht Christoph
Published: September 2024

The complement system and neutrophils play crucial roles in innate immunity. Neutrophils release neutrophil extracellular traps (NETs), which are composed of decondensed DNA entangled with granular contents, as part of their innate immune function. Mechanisms governing complement-mediated NET formation remain unclear. In this study, we tested a two-step NETosis mechanism, as follows: classical complement-mediated neutrophil activation in serum and subsequent NET formation in serum-free conditions, using neutrophils from healthy donors, endothelial cells, and various assays (Fluo-4AM, DHR123, and SYTOX), along with flow cytometry and confocal microscopy. Our findings reveal that classical complement activation on neutrophils upregulated the membrane-anchored complement regulators CD46, CD55, and CD59. Additionally, complement activation increased CD11b on neutrophils, signifying activation and promoting their attachment to endothelial cells. Complement activation induced calcium influx and citrullination of histone 3 (CitH3) in neutrophils. However, CitH3 formation alone was insufficient for NET generation. Importantly, NET formation occurred only when neutrophils were in serum-free conditions. In such environments, neutrophils induced NADPH oxidase-dependent reactive oxygen species (ROS) production, leading to NET formation. Hence, we propose that complement-mediated NET formation involves a two-step process, as follows: complement deposition, neutrophil priming, calcium influx, CitH3 formation, and attachment to endothelial cells in serum. This is followed by NADPH-dependent ROS production and NET completion in serum-free conditions. Understanding this process may unveil treatment targets for pathologies involving complement activation and NET formation.
Protein Kinase C-Delta Mediates Cell Cycle Reentry and Apoptosis Induced by Amyloid-Beta Peptide in Post-Mitotic Cortical Neurons
Authors: Wu Ming-Hsuan , Chao A-Ching , Hsieh Yi-Heng , Lien You , Lin Yi-Chun , Yang Ding-I
Published: September 2024

Amyloid-beta peptide (Aβ) is a neurotoxic constituent of senile plaques in the brains of Alzheimer’s disease (AD) patients. The detailed mechanisms by which protein kinase C-delta (PKCδ) contributes to Aβ toxicity is not yet entirely understood. Using fully differentiated primary rat cortical neurons, we found that inhibition of Aβ25-35-induced PKCδ increased cell viability with restoration of neuronal morphology. Using cyclin D1, proliferating cell nuclear antigen (PCNA), and histone H3 phosphorylated at Ser-10 (p-Histone H3) as the respective markers for the G1-, S-, and G2/M-phases, PKCδ inhibition mitigated cell cycle reentry (CCR) and subsequent caspase-3 cleavage induced by both Aβ25-35 and Aβ1-42 in the post-mitotic cortical neurons. Upstream of PKCδ, signal transducers and activators of transcription (STAT)-3 mediated PKCδ induction, CCR, and caspase-3 cleavage upon Aβ exposure. Downstream of PKCδ, aberrant neuronal CCR was triggered by overactivating cyclin-dependent kinase-5 (CDK5) via calpain2-dependent p35 cleavage into p25. Finally, PKCδ and CDK5 also contributed to Aβ25-35 induction of p53-upregulated modulator of apoptosis (PUMA) in cortical neurons. Together, we demonstrated that, in the post-mitotic neurons exposed to Aβs, STAT3-dependent PKCδ expression triggers calpain2-mediated p35 cleavage into p25 to overactivate CDK5, thus leading to aberrant CCR, PUMA induction, caspase-3 cleavage, and ultimately apoptosis.
Advancing Human iPSC-Derived Cardiomyocyte Hypoxia Resistance for Cardiac Regenerative Therapies through a Systematic Assessment of In Vitro Conditioning
Authors: Snyder Caroline A. , Dwyer Kiera D. , Coulombe Kareen L. K.
Published: September 2024

Acute myocardial infarction (MI) is a sudden, severe cardiac ischemic event that results in the death of up to one billion cardiomyocytes (CMs) and subsequent decrease in cardiac function. Engineered cardiac tissues (ECTs) are a promising approach to deliver the necessary mass of CMs to remuscularize the heart. However, the hypoxic environment of the heart post-MI presents a critical challenge for CM engraftment. Here, we present a high-throughput, systematic study targeting several physiological features of human induced pluripotent stem cell-derived CMs (hiPSC-CMs), including metabolism, Wnt signaling, substrate, heat shock, apoptosis, and mitochondrial stabilization, to assess their efficacy in promoting ischemia resistance in hiPSC-CMs. The results of 2D experiments identify hypoxia preconditioning (HPC) and metabolic conditioning as having a significant influence on hiPSC-CM function in normoxia and hypoxia. Within 3D engineered cardiac tissues (ECTs), metabolic conditioning with maturation media (MM), featuring high fatty acid and calcium concentration, results in a 1.5-fold increase in active stress generation as compared to RPMI/B27 control ECTs in normoxic conditions. Yet, this functional improvement is lost after hypoxia treatment. Interestingly, HPC can partially rescue the function of MM-treated ECTs after hypoxia. Our systematic and iterative approach provides a strong foundation for assessing and leveraging in vitro culture conditions to enhance the hypoxia resistance, and thus the successful clinical translation, of hiPSC-CMs in cardiac regenerative therapies.
Environmental Temperature Variation Affects Brain Lipid Composition in Adult Zebrafish (Danio rerio)
Authors: Maffioli Elisa , Nonnis Simona , Negri Armando , Fontana Manuela , Frabetti Flavia , Rossi Anna Rita , Tedeschi Gabriella , Toni Mattia
Published: September 2024

This study delves deeper into the impact of environmental temperature variations on the nervous system in teleost fish. Previous research has demonstrated that exposing adult zebrafish (Danio rerio) to 18 °C and 34 °C for 4 or 21 days induces behavioural changes compared to fish kept at a control temperature of 26 °C, suggesting alterations in the nervous system. Subsequent studies revealed that these temperature conditions also modify brain protein expression, indicating potential neurotoxic effects. The primary aim of this work was to investigate the effects of prolonged exposure (21 days) to 18 °C or 34 °C on the brain lipidomes of adult zebrafish compared to a control temperature. Analysis of the brain lipidome highlighted significant alteration in the relative abundances of specific lipid molecules at 18 °C and 34 °C, confirming distinct effects induced by both tested temperatures. Exposure to 18 °C resulted in an increase in levels of phospholipids, such as phosphatidylethanolamine, alongside a general reduction in levels of sphingolipids, including sphingomyelin. Conversely, exposure to 34 °C produced more pronounced effects, with increases in levels of phosphatidylethanolamine and those of various sphingolipids such as ceramide, gangliosides, and sphingomyelin, alongside a reduction in levels of ether phospholipids, including lysophosphatidylethanolamine ether, phosphatidylethanolamine ether, and phosphatidylglycerol ether, as well as levels of glycolipids like monogalactosyldiacylglycerol. These results, when integrated with existing proteomic and behavioural data, offer new insights into the effects of thermal variations on the nervous system in teleost fish. Specifically, our proteomic and lipidomic findings suggest that elevated temperatures may disrupt mitochondrial function, increase neuronal susceptibility to oxidative stress and cytotoxicity, alter axonal myelination, impair nerve impulse transmission, hinder synapse function and neurotransmitter release, and potentially lead to increased neuronal death. These findings are particularly relevant in the fields of cell biology, neurobiology, and ecotoxicology, especially in the context of global warming.
The Molecular and Immunological Landscape of Meningiomas
Authors: Lotsch Catharina , Warta Rolf , Herold-Mende Christel
Published: September 2024

Meningiomas are the most common primary intracranial tumors in adults and typically have a slow-growing and benign nature. However, there is also a substantial subset of meningiomas that shows aggressive clinical behavior and is refractory to standard treatment modalities, which are still limited to surgery and/or radiotherapy. Despite intensive research, no systemic treatment options are yet available in the clinic for these challenging tumors, resulting in poor patient outcome. Intensive research on the molecular pathogenesis of meningiomas has led to improved diagnostic tools, but so far there is no standardized implementation for the molecular profiling of these tumors for clinical practice. Recent research advances have also focused on the immunophenotyping of meningiomas, leading to several clinical trials examining the use of immune checkpoint blockade therapy in patients with clinically aggressive subtypes. In this review, we aim to summarize the current knowledge on the molecular and immunological landscape of meningiomas in detail and provide current and progressive ideas for future directions.
Neutrophil Extracellular Trap Formation in Advanced Heart Failure Patients—Preliminary Report
Authors: Urbanowicz Tomasz , Olasińska-Wiśniewska Anna , Wojtasińska Ewelina , Filipiak Krzysztof J. , Tomaszewska Małgorzata , Sikora Jędrzej , Krama Marta , Radek Zofia , Grodecki Kajetan , Krasińska-Płachta Aleksandra , Krasińska Beata , Krasiński Zbigniew , Tykarski Andrzej , Jemielity Marek , Rupa-Matysek Joanna
Published: September 2024

In end-stage heart failure, which is characterized by persistent or progressive ventricular dysfunction despite optimal medical therapy, a left ventricular assist device (LVAD) can be beneficial. Congestive heart failure provokes inflammatory and prothrombotic activation. The aim of this study was to evaluate the serum concentration of citrullinated histone 3 (CH3) representing neutrophil extracellular trap (NET) formation in patients referred for LVAD implantation. There were 10 patients with a median age of 61 (57–65) years enrolled in a prospective single-center analysis who underwent LVAD implantation. The CH3 plasma concentration was measured preoperatively and on the 1st and 7th postoperative days, followed by control measurements on the median (Q1–3) 88th (49–143) day. The preoperative CH3 concentration strongly correlated with brain natriuretic peptide (r = 0.879, p < 0.001). Significant differences in CH3 serum concentration were observed between pre- and postoperative measurements, including an increase on the first postoperative day (p < 0.001), as well as a decrease on the seventh day (p = 0.016) and in follow-up (p < 0.001). CH3 concentration, as a marker of NET formation, decreases after LVAD implantation.
The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19
Authors: Drzymała Adam
Published: September 2024

Angiotensin-converting enzyme 2 (ACE2) is considered a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor of high importance, but due to its non-ubiquitous expression, studies of other proteins that may participate in virus internalisation have been undertaken. To date, many alternative receptors have been discovered. Their functioning may provide an explanation for some of the events observed in severe COVID-19 that cannot be directly explained by the model in which ACE2 constitutes the central point of infection. Diabetes mellitus type 2 (T2D) can induce severe COVID-19 development. Although many mechanisms associated with ACE2 can lead to increased SARS-CoV-2 virulence in diabetes, proteins such as basigin (CD147), glucose-regulated protein 78 kDa (GRP78), cluster of differentiation 4 (CD4), transferrin receptor (TfR), integrins α5β1/αvβ3, or ACE2 co-receptors neuropilin 2 (NRP2), vimentin, and even syalilated gangliosides may also be responsible for worsening the COVID-19 course. On the other hand, some others may play protective roles. Understanding how diabetes-associated mechanisms can induce severe COVID-19 via modification of virus receptor functioning needs further extensive studies.
Comparison of Molecular Potential for Iron Transfer across the Placenta in Domestic Pigs with Varied Litter Sizes and Wild Boars
Authors: Kopeć Zuzanna , Starzyński Rafał Radosław , Lenartowicz Małgorzata , Grzesiak Małgorzata , Opiela Jolanta , Smorąg Zdzisław , Gajda Barbara , Nicpoń Jakub , Ogłuszka Magdalena , Wang Xiuying , Mazgaj Rafał , Stankiewicz Adrian , Płonka Wiktoria , Pirga-Niemiec Natalia , Herman Sylwia , Lipiński Paweł
Published: September 2024

Neonatal iron deficiency anemia is prevalent among domestic pigs but does not occur in the offspring of wild boar. The main causes of this disorder in piglets of modern pig breeds are paucity of hepatic iron stores, high birth weight, and rapid growth. Replenishment of fetal iron stores is a direct result of iron transfer efficiency across the placenta. In this study, we attempted to investigate the molecular potential of iron transfer across the placenta as a possible cause of differences between wild boar and Polish Large White (PLW) offspring. Furthermore, by analyzing placentas from PLW gilts that had litters of different sizes, we aimed to elucidate the impact of the number of fetuses on placental ability to transport iron. Using RNA sequencing, we examined the expression of iron-related genes in the placentas from wild boar and PLW gilts. We did not reveal significant differences in the expression of major iron transporters among all analyzed placentas. However, in wild boar placentas, we found higher expression of copper-dependent ferroxidases such as ceruloplasmin, zyklopen, and hephaestin, which facilitate iron export to the fetal circulation. We also determined a close co-localization of ceruloplasmin and zyklopen with ferroportin, the only iron exporter.