bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Invented Spelling Instruction on Literacy Achievement and Writing Motivation
Authors: Schrodt Katie , FitzPatrick Erin , Lee Sungyoon , McKeown Debra , McColloch Alexis , Evert Kimberly
Published: September 2024

Early writing performance strongly predicts long-term literacy performance. It follows that early underachievement in writing is highly correlated with early underachievement in reading. One strategy teachers and students can use to approach writing in the kindergarten classroom is invented spelling. Invented spelling is children’s spontaneous or self-directed attempts to represent words in print by matching sounds to known letters or phonics patterns. A quasi-experimental study was used to evaluate the impact of invented spelling on foundational literacy skills and writing motivation in 63 kindergarten students at a rural school in the Mid-South. The research questions focused on the impact of invented spelling instruction on a variety of literacy outcomes, including foundational skills, spelling, and motivation. The results indicate the significant main effects of invented spelling instruction on students’ invented spelling (p < 0.001), conventional spelling (p < 0.001), complex vocabulary use (p < 0.001, writing motivation (p = 0.040), and writing achievement (p < 0.001). Other outcomes as well as implications and future directions are reported. The invented spelling intervention encouraged low-stake risk taking when writing and removed barriers to writing entry. Allowing time and space for invented spellings means students can focus on communicating their ideas in print without being hindered by the expectation to conform to conventional spellings.
Sea-Based UAV Network Resource Allocation Method Based on an Attention Mechanism
Authors: Mao Zhongyang , Zhang Zhilin , Lu Faping , Pan Yaozong , Zhang Tianqi , Kang Jiafang , Zhao Zhiyong , You Yang
Published: September 2024

As humans continue to exploit the ocean, the number of UAV nodes at sea and the demand for their services are increasing. Given the dynamic nature of marine environments, traditional resource allocation methods lead to inefficient service transmission and ping-pong effects. This study enhances the alignment between network resources and node services by introducing an attention mechanism and double deep Q-learning (DDQN) algorithm that optimizes the service-access strategy, curbs action outputs, and improves service-node compatibility, thereby constituting a novel method for UAV network resource allocation in marine environments. A selective suppression module minimizes the variability in action outputs, effectively mitigating the ping-pong effect, and an attention-aware module is designed to strengthen node-service compatibility, thereby significantly enhancing service transmission efficiency. Simulation results indicate that the proposed method boosts the number of completed services compared with the DDQN, soft actor–critic (SAC), and deep deterministic policy gradient (DDPG) algorithms and increases the total value of completed services.
Sensor-Based Real-Time Monitoring Approach for Multi-Participant Workout Intensity Management
Authors: Saias José , Bravo Jorge
Published: September 2024

One of the significant advantages of technological evolution is the greater ease of collecting and analyzing data. Miniaturization, wireless communication protocols and IoT allow the use of sensors to collect data, with all the potential to support decision making in real time. In this paper, we describe the design and implementation of a digital solution to guide the intensity of training or physical activity, based on heart rate wearable sensors applied to participants in group sessions. Our system, featuring a unified engine that simplifies sensor management and minimizes user disruption, has been proven effective for real-time monitoring. It includes custom alerts during variable-intensity workouts, and ensures data preservation for subsequent analysis by physiologists or clinicians. This solution has been used in sessions of up to six participants and sensors up to 12 m away from the gateway device. We describe some challenges and constraints we face in collecting data from multiple and possibly different sensors simultaneously via Bluetooth Low Energy, and the approaches we follow to overcome them. We conduct an in-depth questionnaire to identify potential obstacles and drivers for system acceptance. We also discuss some possibilities for extension and improvement of our system.
Clop Ransomware in Action: A Comprehensive Analysis of Its Multi-Stage Tactics
Authors: Lee Yongjoon , Lee Jaeil , Ryu Dojin , Park Hansol , Shin Dongkyoo
Published: September 2024

Recently, Clop ransomware attacks targeting non-IT fields such as distribution, logistics, and manufacturing have been rapidly increasing. These advanced attacks are particularly concentrated on Active Directory (AD) servers, causing significant operational and financial disruption to the affected organizations. In this study, the multi-step behavior of Clop ransomware was deeply investigated to decipher the sequential techniques and strategies of attackers. One of the key insights uncovered is the vulnerability in AD administrator accounts, which are often used as a primary point of exploitation. This study aims to provide a comprehensive analysis that enables organizations to develop a deeper understanding of the multifaceted threats posed by Clop ransomware and to build more strategic and robust defenses against them.
Trust-Based Detection and Mitigation of Cyber Attacks in Distributed Cooperative Control of Islanded AC Microgrids
Authors: Taher Md Abu , Tariq Mohd , Sarwat Arif I.
Published: September 2024

In this study, we address the challenge of detecting and mitigating cyber attacks in the distributed cooperative control of islanded AC microgrids, with a particular focus on detecting False Data Injection Attacks (FDIAs), a significant threat to the Smart Grid (SG). The SG integrates traditional power systems with communication networks, creating a complex system with numerous vulnerable links, making it a prime target for cyber attacks. These attacks can lead to the disclosure of private data, control network failures, and even blackouts. Unlike machine learning-based approaches that require extensive datasets and mathematical models dependent on accurate system modeling, our method is free from such dependencies. To enhance the microgrid’s resilience against these threats, we propose a resilient control algorithm by introducing a novel trustworthiness parameter into the traditional cooperative control algorithm. Our method evaluates the trustworthiness of distributed energy resources (DERs) based on their voltage measurements and exchanged information, using Kullback-Leibler (KL) divergence to dynamically adjust control actions. We validated our approach through simulations on both the IEEE-34 bus feeder system with eight DERs and a larger microgrid with twenty-two DERs. The results demonstrated a detection accuracy of around 100%, with millisecond range mitigation time, ensuring rapid system recovery. Additionally, our method improved system stability by up to almost 100% under attack scenarios, showcasing its effectiveness in promptly detecting attacks and maintaining system resilience. These findings highlight the potential of our approach to enhance the security and stability of microgrid systems in the face of cyber threats.
Intelligent Combustion Control in Waste-to-Energy Facilities: Enhancing Efficiency and Reducing Emissions Using AI and IoT
Authors: Shin Dongmin , Lee Jaeho , Son Jihoon , Yun Yongkeun , Song Yoonchan , Song Jaeman
Published: September 2024

Expanding waste-to-energy (WtE) facilities is difficult, and with tightening incineration regulations, improvements in WtE facility operations are required to dispose of waste that is increasing by an average of 4.8% annually. To achieve this, an intelligent combustion control (ICC) system was studied using digital technologies such as the Internet of Things and artificial intelligence to improve the operation of WtE facilities. The ICC system in this study is composed of three modules: perception, decision, and control. Perception: collecting and visualizing digital data on the operating status of WtE facilities; Decision: using AI to propose optimal operation methods; Control: automatically controlling the WtE facility according to the AI-suggested optimization methods. The ICC system was applied to the “G” WtE facility, a solid waste WtE facility operating in Gyeonggi province, Republic of Korea, and the digital data collected over six months showed high quality, with low delay and a data loss rate of only 0.12%. Additionally, in January 2024, the ICC system was used to automatically control the second forced draft fan and induced draft fan over a four-day period. As a result, the incinerator flue gas temperature decreased by 0.66%, steam flow rate improved by 2.41%, power generation increased by 3.09%, CO emissions were reduced by 60.72%, and NOx emissions decreased by 7.33%. Future research will expand the ICC system to include the automatic control of the first forced draft fan and the operation time of the stoker.
Optimised Two-Layer Configuration of SESS-CCHP System Considering Wind and Light Output Correlation and Load Sensitivity
Authors: Cai Mingxi , Zeng Tiejun , Zeng Linjun , Zhou Xinying , Huang Xin
Published: September 2024

With the gradual depletion of fossil energy sources and the diversification of users’ energy demand, combined cooling, heating and power (CCHP) microgrids have become a hot technology to improve energy efficiency and promote efficient and synergistic energy operation. However, the uncertainty and correlation of wind power and photovoltaic (PV) outputs have posed a great challenge to the reliability of CCHP system operation, so CCHP systems are often equipped with energy storage devices to improve system flexibility to ensure the reliability of energy supply. However, system-owned reserves still have shortcomings such as high investment O&M costs and large space requirements. As an emerging model, “shared energy storage” can reduce the investment pressure of users and open up new ways for the economic and stable operation of CCHP systems. Therefore, based on the scenario of wind and solar power correlation and considering different types of load flexibility, this paper proposes to construct a shared energy storage station (SESS)-CCHP double-layer synergistic optimal allocation model. The model incorporates the consideration of the actual operation strategy of the CCHP system in the planning stage of energy storage. An example analysis shows that SESS reduces the total operating cost of the CCHP system by 25.96% and improves the new energy consumption rate by 10.46% compared with no energy storage. Compared with the system independently configured with energy storage, the cost saving is 2.14%, thus validating the effectiveness of the proposed model.
Dynamic Analysis of CO2 Emissions and Their Determinants in the Countries of Central and Eastern Europe
Authors: Augustowski Łukasz , Kułyk Piotr
Published: September 2024

This study addresses the problem of the relationship between the adopted development path and the emission levels of greenhouse gases. The analysis includes the countries of Central and Eastern Europe that joined the EU in 2004–2018. This study used a dynamic analysis due to the nature of the changes taking place, which cannot be assessed in static terms. The results of the research conducted so far for this group of countries have been inconclusive. The countries studied have the aim of accelerating economic growth in order to reduce their distance from other EU countries on the one hand, while attempting to pursue a policy favoring the reduction of greenhouse gas emissions, on the other. The aim of this evaluation was to determine the relationship between GDPs per capita and CO2 emissions and to establish the factors determining this relationship. The results for the whole group showed the presence of N-shaped EKCs. This study showed the importance of energy productivity and demographic factors as well as the pace of GDP growth. This research extended the scope of research on CO2 emissions and their determinants through the use of dynamic methods, as well as the complex course of their relation to GDP per capita in Central Eastern European Countries.
Future Sensemaking Beyond Own Business Self-Interests: Insights from Offshore Wind Energy Innovation Ecosystems
Authors: Brink Tove
Published: September 2024

This research explores how participants in an innovation ecosystem, operating without a focal firm, can collaboratively envision and create societal value beyond their individual business goals. Using participatory action research, the investigation focuses on two cases within the offshore wind energy sector, involving four complementary enterprises and nine enterprises that are both complementary and competitive. The findings suggest that ecosystem participants can collectively pursue opportunities for sustainable value creation that surpass the interests and goals of individual firms. This shift towards a future-oriented, ecosystem-wide perspective was driven by the focus on ecosystem-level value propositions and the dynamic organizing of heterogeneous knowledge, individual behaviors, and organizational behaviors, enabling successful future-oriented sensemaking. The research process highlights practices that led to significant innovation outcomes, such as halving investments, reducing accidents and rework, accelerating operational flow, and fostering long-term investments, like a floating port for installation and maintenance improvements. This study enhances understanding of how future-oriented sensemaking in innovation ecosystems without a focal firm can drive innovation and societal value creation, offering insights for practitioners, academics, and policymakers on governance and collaborative efforts to enable value creation in innovation ecosystems.
On the Absorption of γ-Radiation by Absorbers with a Thickness Equal to a Multiple of the Mean Free Path and Analogies with Standing Waves in a Sound Resonance Tube
Authors: Adamides Eleftherios , Kavadjiklis Andreas , Koutroubas Pavlos S. , Moshonas Nikolaos , Pagiatakis Gerasimos
Published: September 2024

This article addresses the phenomenon of the decreased absorption of γ-radiation when the thickness of the absorber equals a multiple of the mean free path, as observed in relevant laboratory experiments with various absorbing materials. This phenomenon can be compared with the periodic peaks in intensity in an open-ended sound tube that appear at multiples of half wavelength. This could suggest that there is analogy between the two physical systems that are the γ-ray absorber and the sound wave resonance tube. More similarities between the two systems are also presented.
Modern Insulation Materials for Sustainability Based on Natural Fibers: Experimental Characterization of Thermal Properties
Authors: Anwajler Beata
Published: September 2024

The recycling of materials is in line with the policy of a closed-loop economy and is currently an option for managing waste in order to reuse it to create new products. To this end, 3D printing is being used to produce materials not only from pure polymers but also from their composites. Further development in this field seems interesting and necessary, and the use of recycled materials will help to reduce waste and energy consumption. This article deals with the use of degradable waste materials for the production of insulating materials by 3D printing. For the study, samples with different numbers of layers (one and five), composite thickness (20, 40, 60, 80, and 100 mm) and composition (including colored resins that were transparent, black, gray, and metallized, as well as resins that were colored gray using soybean oil and gray using natural fibers) were made. The role of natural fillers was played by glycerin and biomass ash with a weight ratio of 5%. The finished materials were tested, and the values of the coefficient of thermal resistance and heat transfer were determined. The best thermal properties among the tested materials were distinguished by a five-layer sample made of soybean-oil-based resin with a thickness of 100 mm. This sample’s heat transfer coefficient was: 0.16 W/m2K. As a material for thermal insulation in 3D printing technology, biodegradable components have great potential.
Categorising Subjective Perceptions of Middle-Aged Breast Cancer Patients Using Q Methodology
Authors: Shim Min-Jeung , Lee Song-Yi , Ha Oh-Sun
Published: September 2024

Background/Objectives: This study explores the characteristics of different perception types in middle-aged female breast cancer patients and proposes psychological counselling interventions tailored to each type. Methods: The study used the Q methodology, starting with the construction of 40 Q samples and 39 P samples. Results: We categorised middle-aged female patients’ subjective perceptions of battling breast cancer into five types along a spectrum: Type 1, ‘Embracing a New Life’; Type 2, ‘Finally Focusing on Myself’; Type 3, ‘Struggling Amidst Confusion’; Type 4, ‘Withdrawing in Despair’; and Type 5, ‘Pushed to the Edge of Fear’. Conclusions: This study revealed that the subjective experiences of middle-aged female breast cancer patients range on a spectrum from post-traumatic growth to post-traumatic stress disorder (PTSD). Based on these findings, this study discusses the characteristics and significance of each subjectivity type and suggests implications and directions for future research.
Potentials in Using VR for Facilitating Geography Teaching in Classrooms: A Systematic Review
Authors: Czimre Klára , Teperics Károly , Molnár Ernő , Kapusi János , Saidi Ikram , Gusman Deddy , Bujdosó Gyöngyi
Published: September 2024

The application of virtual reality (VR) in geography education is regarded as a progressive and proactive method that has still not gained sufficient attention in the educational policy in Hungary. The aim of our review is to find the ways and means to make it happen. We selected 47 works that are closely linked to geography teaching and analyzed their bibliometric (authorship and journal characteristics, types of works and applied methods, keywords, referencing, and co-citation networks) and contextual characteristics (research objectives, demographic, gender and social background, hardware and software specifications, advantages and disadvantages, conclusions, and predictions) which we expected to help us to understand the slow implementation and undeserved marginalization of VR in the curricular geography education. We used a mixed-method research analysis combining elements of quantitative and qualitative analysis using inductive reasoning. Our preliminary assumption that the application of VR technology is an effective and useful way of teaching geography was proved by our findings. The methods used by the authors of the reviewed empirical works, together with the recommended future research topics and strategies, can be applied to future empirical research on the use of VR in geography education.
MIND Diet Impact on Multiple Sclerosis Patients: Biochemical Changes after Nutritional Intervention
Authors: Navarrete-Pérez Ainoa , Gómez-Melero Sara , Escribano Begoña Mª , Galvao-Carmona Alejandro , Conde-Gavilán Cristina , Peña-Toledo Mª Ángeles , Villarrubia Noelia , Villar Luisa Mª , Túnez Isaac , Agüera-Morales Eduardo , Caballero-Villarraso Javier
Published: September 2024

There is substantial evidence supporting the neuroprotective effects of the MIND diet in neurodegenerative diseases like Parkinson’s and Alzheimer’s. Our aim was to evaluate the impact of a nutritional intervention (NI) with this diet on multiple sclerosis (MS) patients. The study was conducted in two stages. In the first stage, two groups were included: MS patients before the NI (group A) and healthy control subjects (group B). In this stage, groups (A) and (B) were compared (case–control study). In the second stage, group (A) was assessed after the NI, with comparisons made between baseline and final measurements (before-and-after study). In the case–control stage (baseline evaluation), we found significant differences in fatigue scores (p < 0.001), adherence to the MIND diet (p < 0.001), the serum levels of brain-derived neurotrophic factor (BDNF) (p < 0.001), and higher oxidative status in the MS group, with lower levels of reduced glutathione (p < 0.001), reduced/oxidised glutathione ratio (p < 0.001), and elevated levels of lipoperoxidation (p < 0.002) and 8-hydroxy-2′-deoxyguanosine (p < 0.025). The before-and-after intervention stage showed improvements in fatigue scores (p < 0.001) and physical quality-of-life scores (MSQOL-54) (p < 0.022), along with decreases in the serum levels of glial-derived neurotrophic factor (GDNF) (p < 0.041), lipoperoxidation (p < 0.046), and 8-hydroxy-2′-deoxyguanosine (p < 0.05). Consumption of the MIND diet is linked to clinical and biochemical improvement in MS patients.
Enhancing Therapeutic Response and Overcoming Resistance to Checkpoint Inhibitors in Ovarian Cancer through Cell Cycle Regulation
Authors: Wang Shiqi , Luo Chenggui , Guo Jiaqing , Hu Rui , Shen Binglin , Lin Fangrui , Zhang Chenshuang , Liao Changrui , He Jun , Wang Yiping , Qu Junle , Liu Liwei
Published: September 2024

Tumor cells invade normal surrounding tissues through continuous division. In this study, we hypothesized that cell cycle regulation changes the immune efficacy of ovarian cancer. To investigate this hypothesis, a Förster resonance energy transfer (FRET) sensor was constructed to characterize the cell activity in real time. Cell shrinkage caused by apoptosis induces the aggregation of proteins on the cell membrane, leading to variations in the fluorescence lifetime of FRET sensors. Moreover, we tracked cell activity across various cycles following co-culture with an immune checkpoint inhibitor. Consequently, we assessed how cell cycle regulation influences immunotherapy in a tumor mouse model. This approach, which involves inhibiting typical cell cycle processes, markedly enhances the effectiveness of immunotherapy. Our findings suggest that modulating the cycle progression of cancer cells may represent a promising approach to enhance the immune response of ovarian cancer cells and the efficacy of immunotherapy based on immune checkpoint inhibitors.
Predicting Antidiabetic Peptide Activity: A Machine Learning Perspective on Type 1 and Type 2 Diabetes
Authors: Cai Kaida , Zhang Zhe , Zhu Wenzhou , Liu Xiangwei , Yu Tingqing , Liao Wang
Published: September 2024

Diabetes mellitus (DM) presents a critical global health challenge, characterized by persistent hyperglycemia and associated with substantial economic and health-related burdens. This study employs advanced machine-learning techniques to improve the prediction and classification of antidiabetic peptides, with a particular focus on differentiating those effective against T1DM from those targeting T2DM. We integrate feature selection with analysis methods, including logistic regression, support vector machines (SVM), and adaptive boosting (AdaBoost), to classify antidiabetic peptides based on key features. Feature selection through the Lasso-penalized method identifies critical peptide characteristics that significantly influence antidiabetic activity, thereby establishing a robust foundation for future peptide design. A comprehensive evaluation of logistic regression, SVM, and AdaBoost shows that AdaBoost consistently outperforms the other methods, making it the most effective approach for classifying antidiabetic peptides. This research underscores the potential of machine learning in the systematic evaluation of bioactive peptides, contributing to the advancement of peptide-based therapies for diabetes management.
Potential Involvements of Cilia-Centrosomal Genes in Primary Congenital Glaucoma
Authors: Pyatla Goutham , Kabra Meha , Mandal Anil K. , Zhang Wei , Mishra Ashish , Bera Samir , Rathi Sonika , Patnaik Satish , Anthony Alice A. , Dixit Ritu , Banerjee Seema , Shekhar Konegari , Marmamula Srinivas , Kaur Inderjeet , Khanna Rohit C. , Chakrabarti Subhabrata
Published: September 2024

Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1, LTBP2, and TEK and their interactions with MYOC, FOXC1, and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes (MYOC) and perform ciliary functions (TEK), we explored the involvement of a core centrosomal protein, CEP164, which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E, which synergistically interacts with CEP164, and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis.
Polyamine Pathway Inhibitor DENSPM Suppresses Lipid Metabolism in Pheochromocytoma Cell Line
Authors: Ghayee Hans K. , Costa Kaylie A. , Xu Yiling , Hatch Heather M. , Rodriguez Mateo , Straight Shelby C. , Bustamante Marian , Yu Fahong , Smagulova Fatima , Bowden John A. , Tevosian Sergei G.
Published: September 2024

Pheochromocytomas (PCCs) are tumors arising from chromaffin cells in the adrenal medulla, and paragangliomas (PGLs) are tumors derived from extra-adrenal sympathetic or parasympathetic paraganglia; these tumors are collectively referred to as PPGL cancer. Treatment for PPGL primarily involves surgical removal of the tumor, and only limited options are available for treatment of the disease once it becomes metastatic. Human carriers of the heterozygous mutations in the succinate dehydrogenase subunit B (SDHB) gene are susceptible to the development of PPGL. A physiologically relevant PCC patient-derived cell line hPheo1 was developed, and SDHB_KD cells carrying a stable short hairpin knockdown of SDHB were derived from it. An untargeted metabolomic approach uncovered an overactive polyamine pathway in the SDHB_KD cells that was subsequently fully validated in a large set of human SDHB-mutant PPGL tumor samples. We previously reported that treatment with the polyamine metabolism inhibitor N1,N11-diethylnorspermine (DENSPM) drastically inhibited growth of these PCC-derived cells in culture as well as in xenograft mouse models. Here we explored the mechanisms underlying DENSPM action in hPheo1 and SDHB_KD cells. Specifically, by performing an RNAseq analysis, we have identified gene expression changes associated with DENSPM treatment that broadly interfere with all aspects of lipid metabolism, including fatty acid (FA) synthesis, desaturation, and import/uptake. Furthermore, by performing an untargeted lipidomic liquid chromatography–mass spectrometry (LC/MS)-based analysis we uncovered specific groups of lipids that are dramatically reduced as a result of DENSPM treatment. Specifically, the bulk of plasmanyl ether lipid species that have been recently reported as the major determinants of cancer cell fate are notably decreased. In summary, this work suggests an intersection between active polyamine and lipid pathways in PCC cells.
Mobilization of Endogenous CD34+/CD133+ Endothelial Progenitor Cells by Enhanced External Counter Pulsation for Treatment of Refractory Angina
Authors: Tartaglia Joseph T. , Eisenberg Carol A. , DeMarco Joseph C. , Puccio Gregory , Tartaglia Christina E. , Hamby Carl V.
Published: September 2024

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (β = −2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.
Genome-Wide Association Study of Resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides
Authors: Li Pinhong , Luo Xia , Zuo Shaozhi , Fu Xiaozhe , Lin Qiang , Niu Yinjie , Liang Hongru , Ma Baofu , Li Ningqiu
Published: September 2024

The disease caused by Largemouth bass ranavirus (LMBV) is one of the most severe viral diseases in largemouth bass (Micropterus salmoides). It is crucial to evaluate the genetic resistance of largemouth bass to LMBV and develop markers for disease-resistance breeding. In this study, 100 individuals (45 resistant and 55 susceptible) were sequenced and evaluated for resistance to LMBV and a total of 2,579,770 variant sites (SNPs-single-nucleotide polymorphisms (SNPs) and insertions–deletions (InDels)) were identified. A total of 2348 SNPs-InDels and 1018 putative candidate genes associated with LMBV resistance were identified by genome-wide association analyses (GWAS). Furthermore, GO and KEGG analyses revealed that the 10 candidate genes (MHC II, p38 MAPK, AMPK, SGK1, FOXO3, FOXO6, S1PR1, IL7R, RBL2, and GADD45) were related to intestinal immune network for IgA production pathway and FoxO signaling pathway. The acquisition of candidate genes related to resistance will help to explore the molecular mechanism of resistance to LMBV in largemouth bass. The potential polymorphic markers identified in this study are important molecular markers for disease resistance breeding in largemouth bass.
Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy
Authors: Salman Badih , Bon Emeline , Delers Perrine , Cottin Steve , Pasho Elena , Ciura Sorana , Sapaly Delphine , Lefebvre Suzie
Published: September 2024

Dysregulated RNA metabolism caused by SMN deficiency leads to motor neuron disease spinal muscular atrophy (SMA). Current therapies improve patient outcomes but achieve no definite cure, prompting renewed efforts to better understand disease mechanisms. The calcium channel blocker flunarizine improves motor function in Smn-deficient mice and can help uncover neuroprotective pathways. Murine motor neuron-like NSC34 cells were used to study the molecular cell-autonomous mechanism. Following RNA and protein extraction, RT-qPCR and immunodetection experiments were performed. The relationship between flunarizine mRNA targets and RNA-binding protein GEMIN5 was explored by RNA-immunoprecipitation. Flunarizine increases demethylase Kdm6b transcripts across cell cultures and mouse models. It causes, in NSC34 cells, a temporal expression of GEMIN5 and KDM6B. GEMIN5 binds to flunarizine-modulated mRNAs, including Kdm6b transcripts. Gemin5 depletion reduces Kdm6b mRNA and protein levels and hampers responses to flunarizine, including neurite extension in NSC34 cells. Moreover, flunarizine increases the axonal extension of motor neurons derived from SMA patient-induced pluripotent stem cells. Finally, immunofluorescence studies of spinal cord motor neurons in Smn-deficient mice reveal that flunarizine modulates the expression of KDM6B and its target, the motor neuron-specific transcription factor HB9, driving motor neuron maturation. Our study reveals GEMIN5 regulates Kdm6b expression with implications for motor neuron diseases and therapy.
Ciliary Function, Antigen Stasis and Asthma
Authors: Marozkina Nadzeya
Published: September 2024

The prevalence of asthma exceeds 3% of the population. Asthma is observed to be more common in children following severe viral lower respiratory illnesses that affect ciliary function, but mechanisms linking ciliary function to asthma pathogenesis have been obscure. Recent data regarding primary ciliary dyskinesia (PCD) may help us to understand the association. Here, I will review what is known about the relationship between ciliary function and asthma. PCD is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33-mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Moreover, variants in genes that affect the function of cilia can be associated with poor lung function, even in the absence of PCD, and with increased asthma severity. The role of antigen stasis on the surface of dysfunctional airway cilia in the pathophysiology of asthma is a novel area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma.
Gallium Uncouples Iron Metabolism to Enhance Glioblastoma Radiosensitivity
Authors: Owusu Stephenson B. , Zaher Amira , Ahenkorah Stephen , Pandya Darpah N. , Wadas Thaddeus J. , Petronek Michael S.
Published: September 2024

Gallium-based therapy has been considered a potentially effective cancer therapy for decades and has recently re-emerged as a novel therapeutic strategy for the management of glioblastoma tumors. Gallium targets the iron-dependent phenotype associated with aggressive tumors by mimicking iron in circulation and gaining intracellular access through transferrin-receptor-mediated endocytosis. Mechanistically, it is believed that gallium inhibits critical iron-dependent enzymes like ribonucleotide reductase and NADH dehydrogenase (electron transport chain complex I) by replacing iron and removing the ability to transfer electrons through the protein secondary structure. However, information regarding the effects of gallium on cellular iron metabolism is limited. As mitochondrial iron metabolism serves as a central hub of the iron metabolic network, the goal of this study was to investigate the effects of gallium on mitochondrial iron metabolism in glioblastoma cells. Here, it has been discovered that gallium nitrate can induce mitochondrial iron depletion, which is associated with the induction of DNA damage. Moreover, the generation of gallium-resistant cell lines reveals a highly unstable phenotype characterized by impaired colony formation associated with a significant decrease in mitochondrial iron content and loss of the mitochondrial iron uptake transporter, mitoferrin-1. Moreover, gallium-resistant cell lines are significantly more sensitive to radiation and have an impaired ability to repair any sublethal damage and to survive potentially lethal radiation damage when left for 24 h following radiation. These results support the hypothesis that gallium can disrupt mitochondrial iron metabolism and serve as a potential radiosensitizer.
Genome-Wide Identification and Expression Analysis of MYB Transcription Factor Family in Response to Various Abiotic Stresses in Coconut (Cocos nucifera L.)
Authors: Si Cheng-Cheng , Li Yu-Bin , Hai Xue , Bao Ci-Ci , Zhao Jin-Yang , Ahmad Rafiq , Li Jing , Wang Shou-Chuang , Li Yan , Yang Yao-Dong
Published: September 2024

Abiotic stresses such as nitrogen deficiency, drought, and salinity significantly impact coconut production, yet the molecular mechanisms underlying coconut’s response to these stresses are poorly understood. MYB proteins, a large and diverse family of transcription factors (TF), play crucial roles in plant responses to various abiotic stresses, but their genome-wide characterization and functional roles in coconut have not been comprehensively explored. This study identified 214 CnMYB genes (39 1R–MYB, 171 R2R3–MYB, 2 3R–MYB, and 2 4R–MYB) in the coconut genome. Phylogenetic analysis revealed that these genes are unevenly distributed across the 16 chromosomes, with conserved consensus sequences, motifs, and gene structures within the same subgroups. Synteny analysis indicated that segmental duplication primarily drove CnMYB evolution in coconut, with low nonsynonymous/synonymous ratios suggesting strong purifying selection. The gene ontology (GO) annotation of protein sequences provided insights into the biological functions of the CnMYB gene family. CnMYB47/70/83/119/186 and CnMYB2/45/85/158/195 were identified as homologous genes linked to nitrogen deficiency, drought, and salinity stress through BLAST, highlighting the key role of CnMYB genes in abiotic stress tolerance. Quantitative analysis of PCR showed 10 CnMYB genes in leaves and petioles and found that the expression of CnMYB45/47/70/83/85/119/186 was higher in 3-month-old than one-year-old coconut, whereas CnMYB2/158/195 was higher in one-year-old coconut. Moreover, the expression of CnMYB70, CnMYB2, and CnMYB2/158 was high under nitrogen deficiency, drought, and salinity stress, respectively. The predicted secondary and tertiary structures of three key CnMYB proteins involved in abiotic stress revealed distinct inter-proteomic features. The predicted interaction between CnMYB2/158 and Hsp70 supports its role in coconut’s drought and salinity stress responses. These results expand our understanding of the relationships between the evolution and function of MYB genes, and provide valuable insights into the MYB gene family’s role in abiotic stress in coconut.
Unfolding Mechanism and Fibril Formation Propensity of Human Prion Protein in the Presence of Molecular Crowding Agents
Authors: Madheswaran Manoj , Ventserova Nataliia , D’Abrosca Gianluca , Salzano Giulia , Celauro Luigi , Cazzaniga Federico Angelo , Isernia Carla , Malgieri Gaetano , Moda Fabio , Russo Luigi , Legname Giuseppe , Fattorusso Roberto
Published: September 2024

The pathological process of prion diseases implicates that the normal physiological cellular prion protein (PrPC) converts into misfolded abnormal scrapie prion (PrPSc) through post-translational modifications that increase β-sheet conformation. We recently demonstrated that HuPrP(90–231) thermal unfolding is partially irreversible and characterized by an intermediate state (β-PrPI), which has been revealed to be involved in the initial stages of PrPC fibrillation, with a seeding activity comparable to that of human infectious prions. In this study, we report the thermal unfolding characterization, in cell-mimicking conditions, of the truncated (HuPrP(90–231)) and full-length (HuPrP(23–231)) human prion protein by means of CD and NMR spectroscopy, revealing that HuPrP(90–231) thermal unfolding is characterized by two successive transitions, as in buffer solution. The amyloidogenic propensity of HuPrP(90–231) under crowded conditions has also been investigated. Our findings show that although the prion intermediate, structurally very similar to β-PrPI, forms at a lower temperature compared to when it is dissolved in buffer solution, in cell-mimicking conditions, the formation of prion fibrils requires a longer incubation time, outlining how molecular crowding influences both the equilibrium states of PrP and its kinetic pathways of folding and aggregation.
Effect of Spermidine on Endothelial Function in Systemic Lupus Erythematosus Mice
Authors: Kim Hyoseon , Massett Michael P.
Published: September 2024

Endothelial dysfunction is common in Systemic Lupus Erythematosus (SLE), even in the absence of cardiovascular disease. Evidence suggests that impaired mitophagy contributes to SLE. Mitochondrial dysfunction is also associated with impaired endothelial function. Spermidine, a natural polyamine, stimulates mitophagy by the PINK1–parkin pathway and counters age-associated endothelial dysfunction. However, the effect of spermidine on mitophagy and vascular function in SLE has not been explored. To address this gap, 9-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned to spermidine treatment (lpr_Spermidine and MpJ_Spermidine) for 8 weeks or as control (lpr_Control and MpJ_Control). lpr_Control mice exhibited impaired endothelial function (e.g., decreased relaxation to acetylcholine), increased markers of inflammation, and lower protein content of parkin, a mitophagy marker, in the thoracic aorta. Spermidine treatment prevented endothelial dysfunction in MRL-lpr mice. Furthermore, aortas from lpr_Spermidine mice had lower levels of inflammatory markers and higher levels of parkin. Lupus phenotypes were not affected by spermidine. Collectively, these results demonstrate the beneficial effects of spermidine treatment on endothelial function, inflammation, and mitophagy in SLE mice. These results support future studies of the beneficial effects of spermidine on endothelial dysfunction and cardiovascular disease risk in SLE.
The Role of Long Non-Coding RNAs in Ovarian Cancer Cells
Authors: Golara Anna , Kozłowski Mateusz , Cymbaluk-Płoska Aneta
Published: September 2024

Among the most deadly malignancies that strike women worldwide, ovarian cancer is still one of the most common. The primary factor affecting a patient’s survival is early lesion discovery. Unfortunately, because ovarian cancer is a sneaky illness that usually manifests as nonspecific symptoms only in advanced stages, its early detection and screening are challenging. A lot of research is being conducted on effective methods of diagnosing and treating ovarian cancer. Recently, non-coding RNAs (ncRNAs) have gained great popularity, which are considered to be the main regulators of many cellular processes, especially those occurring in cancer. LncRNAs are also being studied for their therapeutic use in the treatment of ovarian cancer and their use in diagnostics and as indicators of poor prognosis. In this article, we reviewed lncRNAs described in the literature that may play an important role in ovarian cancer.
TRPA1 Influences Staphylococcus aureus Skin Infection in Mice and Associates with HIF-1a and MAPK Pathway Modulation
Authors: Yadav Manoj , Chaudhary Prem Prashant , Ratley Grace , D’Souza Brandon , Kaur Mahaldeep , Ganesan Sundar , Kabat Juraj , Myles Ian A.
Published: September 2024

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major public health burden. Emerging antibiotic resistance has heightened the need for new treatment approaches for MRSA infection such as developing novel antimicrobial agents and enhancing the host’s defense response. The thermo-ion channels Transient Receptor Potential (TRP-) A1 and V1 have been identified as modulators of S. aureus quorum sensing in cell culture models. However, their effects on in vivo infection control are unknown. In this study, we investigated the therapeutic effect of natural TRP ion channel inhibitors on MRSA skin infection in mice. While deletion of TRPV1 did not affect lesion size or inflammatory markers, TRPA1−/− mice demonstrated significantly reduced infection severity and abscess size. Treatment with natural inhibitors of TRPA1 with or without blockade of TRPV1 also reduced abscess size. Tissue transcriptomic data coupled with immunohistochemistry revealed that TRPA1 inhibition impacted heat shock protein expression (HSP), modulated the HIF-1a and MAPK pathways, and reduced IL4 expression. Additionally, metabolomics data showed an impact on purine and glycosaminoglycan pathways. Multi-omic integration of transcriptomic and metabolic data revealed that diacylglycerol metabolism was the likely bridge between metabolic and immunological impacts. Our findings suggest that TRPA1 antagonism could provide a promising and cost-effective therapeutic approach for reducing the severity of MRSA infection, and presents a novel underlying molecular mechanism.
Nutraceutical Supplementation as a Potential Non-Drug Treatment for Fibromyalgia: Effects on Lipid Profile, Oxidative Status, and Quality of Life
Authors: de la Cruz Cazorla Salvador , Blanco Santos , Rus Alma , Molina-Ortega Francisco Javier , Ocaña Esther , Hernández Raquel , Visioli Francesco , Moral María Luisa del
Published: September 2024

Fibromyalgia (FM) is a chronic syndrome of unknown etiology, although many studies point to inflammation, oxidative stress, and altered mitochondrial metabolism as some of the cornerstones of this disease. Despite its socioeconomic importance and due to the difficulties in diagnosis, there are no effective treatments. However, the use of non-drug treatments is increasingly becoming a recommended strategy. In this context, the effects of supplementation of FM patients with an olive (poly)phenol, vitamin C, and vitamin B preparation were investigated in this work, analyzing complete blood count, biochemical, lipid, and coagulation profiles, and inflammation and oxidation status in blood samples. To gain a better understanding of the molecular mechanisms and pathways involved in the etiology of FM, a proteomic study was also performed to investigate the mechanisms of action of the supplement. Our results show that the nutraceutical lowers the lipid profile, namely cholesterol, and improves the oxidative status of patients as well as their quality of life, suggesting that this product could be beneficial in the co-treatment of FM. ClinicalTrials.gov (ID: NCT06348537).