bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Stochastic Controller for Efficient Power Extraction from Small-Scale Wind Energy Conversion Systems under Random Load Consumption
Authors: Tighirt Abdelhakim , Aatabe Mohamed , El Guezar Fatima , Bouzahir Hassane , Vargas Alessandro N. , Neretti Gabriele
Published: October 2024

This paper presents an innovative scheme to enhance the efficiency of power extraction from wind energy conversion systems (WECSs) under random loads. The study investigates how stochastic load consumption, modeled and predicted using a Markov chain process, impacts WECS efficiency. The suggested approach regulates the rectifier voltage rather than the rotor speed, making it a sensorless and reliable method for small-scale WECSs. Nonlinear WECS dynamics are represented using Takagi–Sugeno (TS) fuzzy modeling. Furthermore, the closed-loop system’s stochastic stability and recursive feasibility are guaranteed regardless of random load changes. The performance of the suggested controller is compared with the traditional perturb-and-observe (P&O) algorithm under varying wind speeds and random load variations. Simulation results show that the proposed approach outperforms the traditional P&O algorithm, demonstrating higher tracking efficiency, rapid convergence to the maximum power point (MPP), reduced steady-state oscillations, and lower error indices. Enhancing WECS efficiency under unpredictable load conditions is the primary contribution, with simulation results indicating that the tracking efficiency increases to 99.93%.
Car Sales, Fuel Economy and Decarbonization in Mexico
Authors: Bonilla David , Banister David , Caballero Castrillo Adriana
Published: October 2024

The car market in Mexico has undergone substantial change over the last twenty years, as sales have increased dramatically and as policy measures have been introduced to improve fuel economy so that decarbonization targets can be achieved. The argument presented in this paper is that overall fuel economy is driven by vehicle sales and the fuel economy standards imposed. In addition, this picture is complicated by the purchasing preferences of buyers, and this might reduce the effectiveness of the policy measures introduced. A case study approach allows analysis of the shifts in transport policy (2003–2020) to be undertaken by linking the fuel consumption of cars (L/100 km) to the purchasing patterns of consumers, and from this estimate the levels of CO2 emissions. From the empirical analysis, it is found that, although there have been fuel economy gains every year, this is countered by (a) increasing sales of SUVs, and (b) a car market that is increasingly being dominated by larger cars. The current fuel standards are not sufficient to control the continued growth in fuel consumption, and levels of carbon emissions are continuing to increase. In conclusion, tighter emissions standards are needed, together with stronger governance structures and a range of further policy measures to improve car efficiencies and limit growth of the use of larger vehicles.
Modelling of Glass Soiling Due to Air Pollution Exposure at Urban and National Scales: Coimbra (Portugal) Case Study
Authors: Batista Nathale , Pina Noela , Tchepel Oxana
Published: October 2024

Impacts of air pollution are not limited to human health and ecosystems, but are also important for building materials. The main objective of this study is the quantification and mapping of air pollution effects on the materials, namely the soiling effect of modern glass. An integrated modelling approach was implemented to quantify and analyze the spatial distribution of glass soiling due to exposure to air pollution. The methodology is based on an integrated modelling approach (transportation-emissions-dispersion modelling) applied with high spatial resolution for Coimbra (Portugal) urban area and compared with national scale modelling, showing the important contribution of local pollution sources affecting spatial variability in the soiling effect. Air quality data from CAMS (Copernicus Atmosphere Monitoring Service) were used to quantify the soiling effect at national scale. The results are presented and analyzed in terms of haze. The results obtained at national scale suggest that the average time to reach a 1% haze is 320 days, and this time is reduced to 180 days in the most affected areas. However, urban scale modelling applied with a detailed characterization of local pollution sources in Coimbra provides significantly different results and reveals that in the most affected areas, near road traffic, 1% haze could be reached in approximately 80 days. The methodology proposed and implemented in this study provides relevant information for the maintenance and preservation of building materials and highlights the importance of integrated modelling with high spatial resolution for the assessment of the soiling effect in the built environment.
Mobility–Multihoming Duality
Authors: Yanagida Ryo , Bhatti Saleem Noel
Published: October 2024

In modern Internet-based communication, especially mobile systems, a mobile node (MN) will commonly have more than one possibility for Internet Protocol (IP) connectivity. For example, an MN such as a smartphone may be associated with an IEEE 802.11 network at a site while also connected to a cellular base station for 5G. In such a scenario, the smartphone might only be able to utilise the IEEE 802.11 network, not making use of the cellular connectivity simultaneously. Currently, IP does not allow applications and devices to easily utilise multiple IP connectivity opportunities—multihoming for the MN—without implementing special mechanisms to manage them. We demonstrate how the use of the Identifier Locator Network Protocol (ILNP), realised as an extension to IPv6, can enable mobility with multihoming using a duality mechanism that treats mobility and multihoming as the same logical concept. We present a network layer solution that does not require any modification to transport protocols, can be implemented using existing application programming interfaces (APIs), and can work for any application. We have evaluated our approach using an implementation in Linux and a testbed. The testbed consisted of commercial equipment to demonstrate that our approach can be used over existing network infrastructure requiring only normal unicast routing for IPv6.
Influence of Genetic and Non-Genetic Factors on the Physical and Mechanical Properties of Mongolian Cashmere Fiber Properties
Authors: Mahjoub Wafa , Ukhnaa Sarangoo , Drean Jean-Yves , Harzallah Omar
Published: October 2024

Cashmere is widely acclaimed as one of the most luxurious textile fibers. Mongolia, a major player in cashmere production and processing, is key to this industry. Despite the rich history of cashmere, there is limited research on cashmere fiber properties, which are essential in producing high-quality garments. This study aims to improve our understanding of cashmere fibers’ physical and mechanical properties and to assess how genetic and non-genetic factors affect these characteristics. We analyzed key fiber characteristics, including scale morphology, and the physical and mechanical properties (such as fineness, length parameters, stress, and strain) in 11 samples from Mongolian goats of varying areas, breeds, ages, and genders. Through detailed statistical analysis, our experimental results revealed that both genetic and non-genetic factors significantly affect fiber fineness and the specific energy of rupture. Additionally, we observed that the influence of these factors can inform better classification systems for raw cashmere and enhance the determination of the fiber’s spinability limit.
Microwave-Assisted vs. Conventional Extraction of Moringa oleifera Seed Oil: Process Optimization and Efficiency Comparison
Authors: Souza Danivia Endi Santana , Melo Jéssica Jessi Carvalho de , Santos Fernanda Franca dos , Vasconcelos Ana Luíza dos Santos , Jesus Adriana dos Santos de , Freitas Lisiane dos Santos , Souza Ranyere Lucena de , Soares Cleide Mara Faria
Published: October 2024

This study aims to evaluate the effectiveness of microwave-assisted and conventional extraction using ethanol, hexane, and petroleum ether as solvents, and to optimize the process for extracting oil from Moringa oleifera Lam. seeds, with a focus on improving food-grade oil production. Response surface methodology (RSM) was applied to enhance the extraction process of the oil. Central composite rotational design (CCRD) was used to analyze the impact of solid–liquid ratio (x1), power (x2), and temperature (x3) on oil yield. The optimization identified the optimal conditions as a solid/liquid ratio of 1:38, power of 175 W, and temperature of 50 °C, achieving a 42% oil yield. Notably, the microwave-assisted extraction reduced the processing time from 8 h (using conventional Soxhlet extraction) to just 1 h. Conventional extraction with hexane and petroleum ether was also performed for comparison, resulting in similar oil content and fatty acid profiles, predominantly, oleic acid. FTIR analysis confirmed that the microwave-extracted oil contained fatty acids and had similar characteristics to the conventionally extracted oil. Thus, the use of ethanol as a green solvent in the microwave has shown significant improvement in terms of time and energy savings compared to the Soxhlet method with toxic solvents. This study concludes that microwave-assisted extraction with ethanol provides a more energy efficient, environmentally friendly, and time-saving alternative for food-grade oil production, aligning with advancements in food engineering and production.
Thermodynamically Consistent Evolution Equations in Continuum Mechanics
Authors: Morro Angelo
Published: October 2024

This paper addresses the modelling of material behaviour in terms of differential (or rate) equations. To comply with the objectivity principle, recourse is made to invariant fields in the Lagrangian description or to objective time derivatives in the Eulerian description. The thermodynamic consistency is investigated in terms of the Clausius–Duhem inequality with two unusual features. Firstly, the (non-negative) entropy production is viewed as a constitutive function per se. Secondly, the inequality is viewed as a constraint on the pertinent fields and it is solved by using a representation formula, which allows for the the admissibility of a class of models. For definiteness, models of heat conduction are established, within Lagrangian descriptions, while models of the Navier–Stokes–Voigt fluid are investigated within Eulerian descriptions. In connection with thermo-viscous fluids, evolution equations are investigated within the Eulerian description. It is shown that the thermodynamic consistency is compatible with both objective and non-objective evolution equations.
Finite Nuclear Size Effect on the Relativistic Hyperfine Splittings of 2s and 2p Excited States of Hydrogen-like Atoms
Authors: Franzke Katharina Lorena , Gerstmann Uwe
Published: October 2024

Hyperfine splittings play an important role in quantum information and spintronics applications. They allow for the readout of the spin qubits, while at the same time providing the dominant mechanism for the detrimental spin decoherence. Their exact knowledge is thus of prior relevance. In this work, we analytically investigate the relativistic effects on the hyperfine splittings of hydrogen-like atoms, including finite-size effects of the nucleis’ structure. We start from exact solutions of Dirac’s equation using different nuclear models, where the nucleus is approximated by (i) a point charge (Coulomb potential), (ii) a homogeneously charged full sphere, and (iii) a homogeneously charged spherical shell. Equivalent modelling has been done for the distribution of the nuclear magnetic moment. For the 1s ground state and 2s excited state of the one-electron systems H1, H2, H3, and He+3, the calculated finite-size related hyperfine shifts are quite similar for the different structure models and in excellent agreement with those estimated by comparing QED and experiment. This holds also in a simplified approach where relativistic wave functions from a Coulomb potential combined with spherical-shell distributed nuclear magnetic moments promises an improved treatment without the need for an explicit solution of Dirac’s equation within the nuclear core. Larger differences between different nuclear structure models are found in the case of the anisotropic 2p3/2 orbitals of hydrogen, rendering these excited states as promising reference systems for exploring the proton structure.
Multimodal Signal Retiming Projects: A Survey-Based Exploration of Traffic Signal Professionals’ Practices and Challenges
Authors: Ardalan Taraneh , Magalotti Mark Joseph , Stevanovic Aleksandar
Published: October 2024

In the realm of traffic signal operations, the Signal Timing Manual second edition (STM2) serves as a foundational guide for professionals engaged in multimodal signal retiming projects. However, it is acknowledged that the STM2 has its limitations, and real-world conditions often necessitate adaptations in the established procedures. Considering this context, this research endeavors to bridge this gap by conducting a comprehensive survey aimed at traffic signal professionals. This study presents the findings of a comprehensive survey conducted among traffic signal professionals to explore the methodologies, challenges, and practices involved in multimodal signal retiming projects. The survey aimed to obtain detailed insights into the current state of signal retiming, the types of data and tools utilized, and the adaptations necessary to address the complexities of multimodal urban transportation networks. The survey highlights and summarizes responses from 36 professionals across North America, providing insight into both the common strategies and unique challenges faced by those responsible for optimizing signal timings in diverse and dynamic urban environments. The survey results reveal a reliance on diverse tools and data types for signal optimization, highlighting the complexities of accommodating different transportation needs. The findings underscore the importance of tailored approaches and advanced technologies in enhancing signal retiming processes. The insights gained from this study will inform future strategies and enhance the effectiveness of signal retiming procedures in urban areas, thereby contributing to improved traffic management and multimodal transportation efficiency.
Hydrogels with Essential Oils: Recent Advances in Designs and Applications
Authors: Chelu Mariana
Published: October 2024

The innovative fusion of essential oils with hydrogel engineering offers an optimistic perspective for the design and development of next-generation materials incorporating natural bioactive compounds. This review provides a comprehensive overview of the latest advances in the use of hydrogels containing essential oils for biomedical, dental, cosmetic, food, food packaging, and restoration of cultural heritage applications. Polymeric sources, methods of obtaining, cross-linking techniques, and functional properties of hydrogels are discussed. The unique characteristics of polymer hydrogels containing bioactive agents are highlighted. These include biocompatibility, nontoxicity, effective antibacterial activity, control of the sustained and prolonged release of active substances, optimal porosity, and outstanding cytocompatibility. Additionally, the specific characteristics and distinctive properties of essential oils are explored, along with their extraction and encapsulation methods. The advantages and disadvantages of these methods are also discussed. We have considered limitations due to volatility, solubility, environmental factors, and stability. The importance of loading essential oils in hydrogels, their stability, and biological activity is analyzed. This review highlights through an in-depth analysis, the recent innovations, challenges, and future prospects of hydrogels encapsulated with essential oils and their potential for multiple applications including biomedicine, dentistry, cosmetics, food, food packaging, and cultural heritage conservation.
Good People Do Not Eat Others?! Moral Ambiguity in Japanese Fairytales from the Late Nineteenth Century
Authors: Gao Tian
Published: October 2024

In 2015, the Japanese public broadcaster NHK aired an educational series that re-examined traditional fairy tales by putting their characters on trial for their immoral behavior, such as revenge, violence, and dishonesty. These tales, rooted in premodern Japanese folklore, were widely available in various book formats by the late nineteenth century and, unlike modern adaptations, they did not sanitize violence or evil. This study analyzes four miniature picture books from the late nineteenth century that recount the story, Kachikachi yama (The Crackling Mountain). This analysis focuses on both verbal and visual representations of good and evil, with attention to themes of loyalty, filial piety, and virtuous revenge. The findings reveal that these picture books presented young readers with complex moral lessons, where the boundaries between good and evil were blurred. Additionally, they illuminate the prevailing image of children during that era, depicting them as “little adults” expected to be educated and prepared for the practical realities of the adult world.
The Impact of Caregiver Affiliate Stigma on the Psychosocial Well-Being of Caregivers of Individuals with Neurodegenerative Disorders: A Scoping Review
Authors: Becerra Carrillo Nelly , Guasconi Massimo , Barello Serena
Published: October 2024

Background. Caregiver affiliate stigma concerning neurodegenerative disorders (NDDs) profoundly affects caregivers’ well-being, though its full impact remains to be fully elucidated. Objectives. This scoping review aims to consolidate the current knowledge on caregiver affiliate stigma related to NDDs, explore its connection to caregiver psychosocial well-being, and pinpoint the gaps in the existing research. Methods. Adhering to the PRISMA-ScR guidelines, a comprehensive search of five databases was conducted for peer-reviewed, English language studies focusing on caregiver-affiliated stigma in relation to NDDs. Results. The initial search yielded 9033 articles, with 19 meeting the inclusion criteria after rigorous screening. Bronfenbrenner’s ecological systems theory was employed to analyze various stigma conceptualizations, including public, courtesy, affiliate, and family stigma. Analysis revealed a correlation between elevated levels of affiliate stigma and increased caregiver burden, deteriorated mental health outcomes, and diminished quality of life. The internalization of stigma was found to vary across demographic groups, influenced by factors such as education level and social support. The review also highlighted the mediating role of coping strategies and the protective function of social support against stigma internalization. Conclusions, These findings underscore the necessity for targeted, culturally sensitive interventions that address caregiver affiliate stigma across multiple ecological levels. This review contributes to a more nuanced understanding of caregiver affiliate stigma in relation to NDDs, laying the groundwork for future research and intervention development aimed at enhancing caregiver well-being in diverse cultural contexts.
The Real-World Outcomes of Relapsed/Refractory Multiple Myeloma Treated with Elotuzumab, Pomalidomide, and Dexamethasone
Authors: Nakayama Hitomi , Aisa Yoshinobu , Ito Chisako , Sakurai Aki , Nakazato Tomonori
Published: October 2024

Introduction: A combination of elotuzumab, pomalidomide, and dexamethasone (EPd) was approved for the treatment of relapsed/refractory multiple myeloma (RRMM) following the ELOQUENT-3 phase II clinical trial. However, the clinical experience with this therapy is still limited. In this retrospective study, we analyzed the efficacy and safety of EPd in a real-world cohort of RRMM patients. Patients and Methods: The medical records of 22 patients who received EPd for RRMM at Yokohama Municipal Citizen’s Hospital (Japan) between January 2020 and July 2021 were reviewed. Results: The median age of our cohort was 73.5 years. The overall response rate was 55%. With a median follow-up of 20.2 months, the median progression-free survival (PFS) was 9.1 months (95% confidence interval [CI], 2.5–23.0 months). The median PFS was shorter in patients with a poor performance status (PS) than in those with favorable PS (2.5 vs. 10.8 months; p < 0.01). Patients with prior daratumumab had significantly shorter PFS than those without prior daratumumab (2.1 vs. 23.0 months; p < 0.01). Additionally, patients with prior pomalidomide had significantly shorter PFS (1.7 vs. 10.3 months; p < 0.01). In the multivariate analysis, poor PS (hazard ratio [HR] = 4.1, 95% CI: 1.1–15.6; p = 0.04) and prior exposure to daratumumab (HR = 3.8, 95% CI: 1.1–13.8; p = 0.04) remained significantly associated with shorter PFS. Conclusions: The results of our study suggest that EPd is an active and well-tolerated regimen in RRMM, even in real-world patients. Furthermore, EPd may be useful, especially in daratumumab-naïve patients.
Comprehensive Genomic Profiling in Non-Myeloid Hematologic Malignancies Identifies Variants That Can Alter Clinical Practice
Authors: Lin Chenyu , Zhou Katherine I. , Green Michelle F. , Caughey Bennett A. , Strickler John H. , Datto Michael B. , McKinney Matthew S.
Published: October 2024

Background: Comprehensive genomic profiling (CGP) is frequently adopted to direct the clinical care of myeloid neoplasms and solid tumors, but its utility in the care of lymphoid and histiocytic cancers is less well defined. Methods: In this study, we aimed to evaluate the frequency at which mutations identified by CGP altered management in non-myeloid hematologic malignancies. We retrospectively examined the CGP results of 105 samples from 101 patients with non-myeloid hematologic malignancies treated at an academic medical center who had CGP testing between 2014 and 2021. Results: CGP revealed one or more pathogenic or likely pathogenic variant in 92 (88%) of samples and 73 (72%) of tested patients had one or more mutations with diagnostic, prognostic, or therapeutic significance. The identification of a resistance variant resulted in the suspension of the active treatment or affected subsequent treatment choice in 9 (69%) out of 13 patients. However, the presence of a therapy sensitizing variant only led to consideration of a biomarker-directed therapy in 6 (10%) out of 61 patients. Conclusions: Overall, CGP of non-myeloid hematologic malignancies identified clinically significant variants in 72% of patients and resulted in a change in management in 22% of patients.
Blue and Red Light Downconversion Film Application Enhances Plant Photosynthetic Performance and Fruit Productivity of Rubus fruticosus L. var. Loch Ness
Authors: El Horri Hafsa , Vitiello Maria , Braca Alessandra , De Leo Marinella , Guidi Lucia , Landi Marco , Lauria Giulia , Lo Piccolo Ermes , Massai Rossano , Remorini Damiano , Ceccanti Costanza
Published: October 2024

Light downconversion films can modulate incident light wavebands on crops, converting less utilised wavebands in an efficient way. In this experiment, red (conversion of green into red light wavebands), pink (conversion of UV and green into blue and red light but to a smaller degree than red film), and blue (conversion of UV into blue light) light downconversion films were used to cover blackberry plants throughout all phenological stages (from leaf emergence to fruit harvesting). The plants’ physiological and biometric performance, and fruit yield and quality were evaluated. Plants under blue and red films showed a higher net photosynthetic rate with +23.1% and +14.9%, respectively, and a higher stomatal conductance with +56.0% and +23.6%, respectively, with respect to controls, maintaining stability across stages, except for a decrease under the red film during fruiting. Both films significantly boosted the fruit yield, with the red film increasing the fruit number (+49.8%) and the blue film enhancing the berry shape (+10.7) and fresh weight (+36.6). Notably, no significant differences in nutraceutical quality, including total flavonoid and anthocyanin content, were observed. These findings suggest that light downconversion films, particularly red and blue films, can effectively enhance the photosynthetic performance and fruit production in blackberry plants without compromising the fruit quality. Future research on this topic should focus on balancing plant growth, fruit productivity, and enhancing fruit nutraceutical properties.
Genome-Wide Association Analyses Defined the Interplay between Two Major Loci Controlling the Fruit Texture Performance in a Norwegian Apple Collection (Malus × domestica Borkh.)
Authors: Gilpin Liv , Costa Fabrizio , Røen Dag , Alsheikh Muath
Published: October 2024

Increasing consumption of apples (Malus domestica Borkh.) produced in Norway requires the availability of superior cultivars and extended marketability. Favorable texture and slow softening are important traits for consumer appreciation and postharvest performance. Apple texture has been well characterized using both sensory evaluation and instrumental assessments, and major quantitative trait loci (QTL) have been detected. With texture being targeted as an important trait and markers being publicly available, marker-assisted selection has already been implemented into several breeding programs. When focusing solely on a limited set of markers linked to well-investigated major QTLs, most minor-effect QTLs are normally excluded. To find novel potential SNP markers suitable to assist in selection processes, we selected a subset of accessions from a larger apple collection established in Norway based on the favorable alleles of two markers previously associated with texture, enabling the investigation of a minor part of the variance initially masked by the effect of major loci. The subset was employed to conduct a genome-wide association study aiming to search for associations with texture dynamics and retainability. QTL regions related to texture at harvest, postharvest, and for the storage index were identified on chromosomes 3, 12, and 16. Specifically, the SNPs located on chromosome 12 were shown to be potential novel markers for selection of crispness retention during storage, a valuable storability trait. These newly detected QTLs and underlying SNPs will represent a potential set of markers for the selection of the most favorable accessions characterized by superior fruit texture properties in ongoing breeding programs.
Early Chilling Injury Symptom Development and Recovery of Mature Green Banana: Involvement of Ethylene under Different Severities of Chilling Stress
Authors: Chang Lan-Yen , Brecht Jeffrey K.
Published: October 2024

The involvement of stress ethylene in early chilling injury (CI) symptom development of mature-green (MG) banana fruit was examined using the ethylene action inhibitor, 1-methyclopropene (1-MCP). MG banana fruit pretreated with 0 or 50 μg L−1 1-MCP were stored at two chilling temperatures, 5 °C or 10 °C, for 0, 1, 12, or 72 h (different CI stresses), then transferred to 20 °C (rewarming) for 2 d. Irreversible CI symptoms that developed during 72 h storage at 5 or 10 °C included vascular browning and epidermal color parameters (L*, chroma, and hue angle). Some CI symptoms drastically intensified during exposure to 5 or 10 °C for 72 h, even being exacerbated after rewarming. Fruit in the other treatments suffered milder CI, and the recovery response progressed from slight and reversible to severe and irreversible with longer durations of exposure to lower temperatures. The effect of 1-MCP pretreatment was to attenuate the effect of chilling in terms of the CI symptom development (i.e., the browning of sub-epidermal tissues and the increasing of electrolyte efflux) and to promote recovery after rewarming, especially for the fruit stored at 5 °C, indicating the potential involvement of ethylene in membrane structural alterations under CI stress.
Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome
Authors: Deus Marina de Castro , Gadotti Ana Carolina , Dias Erika Sousa , Monte Alegre Júlia Bacarin , Van Spitzenbergen Beatriz Akemi Kondo , Andrade Gabriela Bohnen , Tozoni Sara Soares , Stocco Rebecca Benicio , Olandoski Marcia , Tuon Felipe Francisco Bondan , Pinho Ricardo Aurino , de Noronha Lucia , Baena Cristina Pellegrino , Moreno-Amaral Andrea Novais
Published: October 2024

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1β (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1β and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.
Special Issue “Bioinformatics Study in Human Diseases: Integration of Omics Data for Personalized Medicine”
Authors: Lin Hung-Yu , Chu Pei-Yi
Published: October 2024

The field of bioinformatics has made remarkable strides in recent years, revolutionizing our approach to understanding and treating human diseases [...]
Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis
Authors: Choi Mi Ran , Chang Hye Jin , Heo Jeong-Hyeon , Yum Sun Hyung , Jo Eunae , Kim Miran , Lee Sang-Rae
Published: October 2024

The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without endometriosis (EMS) during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control (CT; P-phase [pCT], n = 8; S-phase [sCT], n = 13) and 23 EMS patients (P-phase [pEMS], n = 13; S-phase [sEMS], n = 12). DElncRNAs and DEmRNAs were analyzed using total RNA-sequencing. In P-phase, expression of NONHSAG019742.2 and NONHSAT120701.2 was significantly higher in EMS than control patients, that of while NONHSAG048398.2 and NONHSAG016560.2 was lower in EMS patients. In S-phase, expression of NONHSAT000959.2, NONHSAT203423.1, and NONHSAG053769.2 was significantly increased in EMS patients, while that of NONHSAG012105.2 and NONHSAG020839.2 was lower. In addition, the expression of HSD11B2, THBS1, GPX3, and SHISA6 was similar to that of neighboring lncRNAs in both P- and S-phases. In contrast, ELP3 and NR4A1, respectively, were up- or downregulated in pEMS tissues. In sEMS, expression of LAMB3 and HIF1A was increased, while expression of PAM was reduced. Our findings on lncRNAs and mRNAs encourage not only exploration of the potential clinical applications of lncRNAs and mRNAs as prognostic or diagnostic biomarkers for EMS but also to gain valuable insights into its pathogenesis.
Computational Study on the Inhibition Mechanisms of the Ziegler-Natta Catalyst in the Propylene Polymerization Process: Part 1 Effects of Acetylene and Methylacetylene
Authors: Hernandez-Fernandez Joaquin , Bello-León Elias , Marquez Edgar
Published: October 2024

Acetylene and methylacetylene are impurities commonly found in the raw materials used for the production of polymers such as polypropylene and polyethylene. Experimental evidence indicates that both acetylene and methylacetylene can decrease the productivity of the Ziegler-Natta catalyst and alter the properties of the resulting polymer. However, there is still a lack of understanding regarding the mechanisms through which these substances affect this process. Therefore, elucidating these mechanisms is crucial to develop effective solutions to this problem. In this study, the inhibition mechanisms of the Ziegler-Natta catalyst by acetylene and methylacetylene are presented and compared with the incorporation of the first propylene monomer (chain initiation) to elucidate experimental effects. The Density Functional Theory (DFT) method was used, along with the B3LYP-D3 functional and the 6-311++G(d,p) basis set. The recorded adsorption energies were −11.10, −13.99, and −0.31 kcal mol−1, while the activation energies were 1.53, 2.83, and 28.36 kcal mol−1 for acetylene, methylacetylene, and propylene, respectively. The determined rate constants were 4.68 × 1011, 5.29 × 1011, and 2.3 × 10−8 M−1 s−1 for acetylene, methylacetylene, and propylene, respectively. Based on these values, it is concluded that inhibition reactions are more feasible than propylene insertion only if an ethylene molecule has not been previously adsorbed, as such an event reinforces propylene adsorption.
Imaging the Raf–MEK–ERK Signaling Cascade in Living Cells
Authors: Shin Young-Chul , Cho Minkyung , Hwang Jung Me , Myung Kyungjae , Kweon Hee-Seok , Lee Zee-Won , Seong Hyun-A. , Lee Kyung-Bok
Published: October 2024

Conventional biochemical methods for studying cellular signaling cascades have relied on destructive cell disruption. In contrast, the live cell imaging of fluorescent-tagged transfected proteins offers a non-invasive approach to understanding signal transduction events. One strategy involves monitoring the phosphorylation-dependent shuttling of a fluorescent-labeled kinase between the nucleus and cytoplasm using nuclear localization, export signals, or both. In this paper, we introduce a simple method to visualize intracellular signal transduction in live cells by exploring the translocation properties of PKC from the cytoplasm to the membrane. We fused bait protein to PKC, allowing the bait (RFP-labeled) and target (GFP-labeled) proteins to co-translocate from the cytoplasm to the membrane. However, in non-interacting protein pairs, only the bait protein was translocated to the plasma membrane. To verify our approach, we examined the Raf–MEK–ERK signaling cascade (ERK pathway). We successfully visualized direct Raf1/MEK2 interaction and the KSR1-containing ternary complex (Raf1/MEK2/KSR1). However, the interaction between MEK and ERK was dependent on the presence of the KSR1 scaffold protein under our experimental conditions.
Quelling the Geometry Factor Effect in Quantum Chemical Calculations of 13C NMR Chemical Shifts with the Aid of the pecG-n (n = 1, 2) Basis Sets
Authors: Rusakov Yuriy Yu. , Semenov Valentin A. , Rusakova Irina L.
Published: October 2024

A root factor for the accuracy of all quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts is the quality of the molecular equilibrium geometry used. In turn, this quality depends largely on the basis set employed at the geometry optimization stage. This parameter represents the main subject of the present study, which is a continuation of our recent work, where new pecG-n (n = 1, 2) basis sets for the geometry optimization were introduced. A goal of this study was to compare the performance of our geometry-oriented pecG-n (n = 1, 2) basis sets against the other basis sets in massive calculations of 13C NMR shielding constants/chemical shifts in terms of their efficacy in reducing geometry factor errors. The testing was carried out with both large-sized biologically active natural products and medium-sized compounds with complicated electronic structures. The former were treated using the computation protocol based on the density functional theory (DFT) and considered in the theoretical benchmarking, while the latter were treated using the computational scheme based on the upper-hierarchy coupled cluster (CC) methods and were used in the practical benchmarking involving the comparison with experimental NMR data. Both the theoretical and practical analyses showed that the pecG-1 and pecG-2 basis sets resulted in substantially reduced geometry factor errors in the calculated 13C NMR chemical shifts/shielding constants compared to their commensurate analogs, with the pecG-2 basis set being the best of all the considered basis sets.
Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study
Authors: Ramírez-Pacheco Arturo , Moreno-Guerrero Silvia Selene , Rocha-Ramírez Luz María , Hernández-Pliego Gabriela , Escobar-Sánchez María Argelia , Reyes-López Alfonso , Sienra-Monge Juan José Luis , Juárez-Villegas Luis Enrique
Published: October 2024

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine’s increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03–0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45–5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068–0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.
Polymers Enhance Chlortetracycline Hydrochloride Solubility
Authors: Zhang Chao , Li Bing , Bai Yubin , Liu Yangling , Zhang Yong , Zhang Jiyu
Published: October 2024

Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A hydrophilic polymer was selected as the carrier, and a solid dispersion was prepared using a medium grinding method, with samples characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and particle size distribution (PSD). To maximize CTC solubility and stability, different polymer types and optimal drug-to-polymer ratios were screened. The solubility of optimized povidone K30 (PVPK30) (1/0.75, w/w)-, hydroxypropyl-β-cyclodextrin (HP-β-CD) (1/2, w/w)-, and gelatin (1/1, w/w)-based solid dispersions was 6.25-, 7.7-, and 3.75-fold higher than that of pure CTC powder, respectively. Additionally, in vitro dissolution studies showed that the gelatin-based solid dispersion had a higher initial dissolution rate. SEM and PS analyses confirmed that this dispersion had smaller and more uniform particles than PVPK30 and HP-β-CD dispersions. Therefore, successful solid polymer dispersion preparations improved the CTC solubility, dissolution rates, and stability, which may have potential as drug delivery systems.
GSP1-111 Modulates the Microglial M1/M2 Phenotype by Inhibition of Toll-like Receptor 2: A Potential Therapeutic Strategy for Depression
Authors: Kim Ryeong-Eun , Mabunga Darine Froy , Boo Kyung-Jun , Kim Dong Hyun , Han Seol-Heui , Shin Chan Young , Kwon Kyoung Ja
Published: October 2024

Neuroinflammation plays a vital role in neurodegenerative diseases and neuropsychiatric disorders, and microglia and astrocytes chiefly modulate inflammatory responses in the central nervous system (CNS). Toll-like receptors (TLRs), which are expressed in neurons, astrocytes, and microglia in the CNS, are critical for innate immune responses; microglial TLRs can regulate the activity of these cells, inducing protective or harmful effects on the surrounding cells, including neurons. Therefore, regulating TLRs in microglia may be a potential therapeutic strategy for neurological disorders. We examined the protective effects of GSP1-111, a novel synthetic peptide for inhibiting TLR signaling, on neuroinflammation and depression-like behavior. GSP1-111 decreased TLR2 expression and remarkably reduced the mRNA expression of inflammatory M1-phenotype markers, including tumor necrosis factor (TNF)α, interleukin (IL)-1β, and IL-6, while elevating that of the M2 phenotype markers, Arg-1 and IL-10. In vivo, GSP1-111 administration significantly decreased the depression-like behavior induced by lipopolysaccharide (LPS) in a forced swim test and significantly reduced the brain levels of M1-specific inflammatory cytokines (TNFα, IL-1β, and IL-6). GSP1-111 prevented the LPS-induced microglial activation and TLR2 expression in the brain. Accordingly, GSP1-111 prevented inflammatory responses and induced microglial switching of the inflammatory M1 phenotype to the protective M2 phenotype. Thus, GSP1-111 could prevent depression-like behavior by inhibiting TLR2. Taken together, our results suggest that the TLR2 pathway is a promising therapeutic target for depression, and GSP1-111 could be a novel therapeutic candidate for various neurological disorders.
Non-Alcoholic Fatty Liver Disease and Coronary Artery Disease: A Bidirectional Association Based on Endothelial Dysfunction
Authors: Ktenopoulos Nikolaos , Sagris Marios , Gerogianni Maria , Pamporis Konstantinos , Apostolos Anastasios , Balampanis Konstantinos , Tsioufis Konstantinos , Toutouzas Konstantinos , Tousoulis Dimitris
Published: October 2024

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. Endothelial dysfunction (EnD) constitutes the main driver in the progression of atherosclerosis and coronary artery disease (CAD). Several pathophysiological alterations and molecular mechanisms are involved in the development of EnD in patients with NAFLD. Our aim is to examine the association of NAFLD and CAD with the parallel assessment of EnD, discussing the pathophysiological mechanisms and the genetic background that underpin this relationship. This review delves into the management of the condition, exploring potential clinical implications and available medical treatment options to facilitate the deployment of optimal treatment strategies for these patients.
Regulatory Role of IL6 in Immune-Related Adverse Events during Checkpoint Inhibitor Treatment in Melanoma
Authors: Singh Krishna P. , Singh Anuj , Wolkenhauer Olaf , Gupta Shailendra Kumar
Published: October 2024

The landscape of clinical management for metastatic melanoma (MM) and other solid tumors has been modernized by the advent of immune checkpoint inhibitors (ICI), including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. While these agents demonstrate efficacy in suppressing tumor growth, they also lead to immune-related adverse events (irAEs), resulting in the exacerbation of autoimmune diseases such as rheumatoid arthritis (RA), ulcerative colitis (UC), and Crohn’s disease (CD). The immune checkpoint inhibitors offer promising advancements in the treatment of melanoma and other cancers, but they also present significant challenges related to irAEs and autoimmune diseases. Ongoing research is crucial to better understand these challenges and develop strategies for mitigating adverse effects while maximizing therapeutic benefits. In this manuscript, we addressed this challenge using network-based approaches by constructing and analyzing the molecular and signaling networks associated with tumor-immune crosstalk. Our analysis revealed that IL6 is the key regulator responsible for irAEs during ICI therapies. Furthermore, we conducted an integrative network and molecular-level analysis, including virtual screening, of drug libraries, such as the Collection of Open Natural Products (COCONUT) and the Zinc15 FDA-approved library, to identify potential IL6 inhibitors. Subsequently, the compound amprenavir was identified as the best molecule that may disrupt essential interactions between IL6 and IL6R, which are responsible for initiating the signaling cascades underlying irAEs in ICI therapies.
Comprehensive Optimization of a Freeze-Drying Process Achieving Enhanced Long-Term Stability and In Vivo Performance of Lyophilized mRNA-LNPs
Authors: Alejo Teresa , Toro-Córdova Alfonso , Fernández Laura , Rivero Andrea , Stoian Andrei Mihai , Pérez Luna , Navarro Victor , Martínez-Oliván Juan , de Miguel Diego
Published: October 2024

The success of mRNA vaccines against SARS-CoV-2 has prompted interest in mRNA-based pharmaceuticals due to their rapid production, adaptability, and safety. Despite these advantages, the inherent instability of mRNA and its rapid degradation in vivo underscores the need for an encapsulation system for the administration and delivery of RNA-based therapeutics. Lipid nanoparticles (LNPs) have proven the most robust and safest option for in vivo applications. However, the mid- to long-term storage of mRNA-LNPs still requires sub-zero temperatures along the entire chain of supply, highlighting the need to develop alternatives to improve mRNA vaccine stability under non-freezing conditions to facilitate logistics and distribution. Lyophilization presents itself as an effective alternative to prolong the shelf life of mRNA vaccines under refrigeration conditions, although a complex optimization of the process parameters is needed to maintain the integrity of the mRNA-LNPs. Recent studies have demonstrated the feasibility of freeze-drying LNPs, showing that lyophilized mRNA-LNPs retain activity and stability. However, long-term functional data remain limited. Herein, we focus on obtaining an optimized lyophilizable mRNA-LNP formulation through the careful selection of an optimal buffer and cryoprotectant and by tuning freeze-drying parameters. The results demonstrate that our optimized lyophilization process maintains LNP characteristics and functionality for over a year at refrigerated temperatures, offering a viable solution to the logistical hurdles of mRNA vaccine distribution.