bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Time to Initiate Therapeutic Hypothermia on Short-Term Neurological Outcomes in Neonates with Hypoxic–Ischemic Encephalopathy
Authors: Dresbach Till , Rigoni Viktoria , Groteklaes Anne , Hoehn Thomas , Stein Anja , Felderhoff-Mueser Ursula , Mueller Andreas , Sabir Hemmen
Published: June 2024

Background: Therapeutic hypothermia is the standard treatment for neonates with hypoxic–ischemic encephalopathy. Preclinical evidence indicates that the time to initiate therapeutic hypothermia correlates with its therapeutic success. This study aims to explore whether there is a correlation between the early initiation of therapeutic hypothermia and improved short-term neurological outcomes in cooled asphyxiated newborns. Methods: A retrospective analysis was conducted, involving 68 neonates from two different neonatal intensive care units. The impact of time to initiate treatment, time to reach the target temperature, and time between initiation and target temperature was correlated with short-term outcomes on MRI. Results: We did not find a significant difference between outcomes regarding the time to start treatment and the time to achieve the target temperature. Interestingly, neonates with a poor outcome were treated on average earlier than neonates with a favorable outcome but required more time to reach the target temperature. Additionally, the study results did not support the hypothesis that a shorter time to initiate treatment would lead to shorter times to achieve the target temperature. Conclusion: Based on our findings, it is recommended to prioritize a thorough evaluation of neonatal encephalopathy before initiating therapeutic hypothermia. Early initiation of treatment should be balanced with the time required for precise assessment to ensure better outcomes.
The Added Value of Statistical Seasonal Forecasts
Authors: Krikken Folmer , Geertsema Gertie , Nielsen Kristian , Troccoli Alberto
Published: June 2024

Seasonal climate predictions can assist with timely preparations for extreme episodes, such as dry or wet periods that have associated additional risks of droughts, fires and challenges for water management. Timely warnings for extreme warm summers or cold winters can aid in preparing for increased energy demand. We analyse seasonal forecasts produced by three different methods: (1) a multi-linear statistical forecasting system based on observations only; (2) a non-linear random forest model based on observations only; and (3) process-based dynamical forecast models. The statistical model is an empirical system based on multiple linear regression that is extended to include the trend over the previous 3 months in the predictors, and overfitting is further reduced by using an intermediate multiple linear regression model. This results in a significantly improved El Niño forecast skill, specifically in spring. Also, the Indian Ocean dipole (IOD) index forecast skill shows improvements, specifically in the summer and autumn months. A hybrid multi-model ensemble is constructed by combining the three forecasting methods. The different methods are used to produce seasonal forecasts (three-month means) for near-surface air temperature and monthly accumulated precipitation seasonal forecast with a lead time of one month. We find numerous regions with added value compared with multi-model ensembles based on dynamical models only. For instance, for June, July and August temperatures, added value is observed in extensive parts of both Northern and Southern America, as well as Europe.
RETRACTED: Hatshan et al. Advanced Binder-Free Electrode Based on CuCo2O4 Nanowires Coated with Polypyrrole Layer as a High-Performance Nonenzymatic Glucose Sensing Platform. Coatings 2021, 11, 1462
Authors: Hatshan Mohammad Rafe , Aslam Sadia , Bokov Dmitry , Ibrahim Ahmed Jaber , Mustafa Yasser Fakri , Davarpanah Afshin , Elveny Marischa , Ali Shafaqat
Published: June 2024

The Coatings Editorial Office retracts the article entitled “Advanced Binder-Free Electrode Based on CuCo2O4 Nanowires Coated with a Polypyrrole Layer as a High-Performance Nonenzymatic Glucose Sensing Platform” [...]
High-Performance Krawtchouk Polynomials of High Order Based on Multithreading
Authors: Flayyih Wameedh Nazar , Al-sudani Ahlam Hanoon , Mahmmod Basheera M. , Abdulhussain Sadiq H. , Alsabah Muntadher
Published: June 2024

Orthogonal polynomials and their moments serve as pivotal elements across various fields. Discrete Krawtchouk polynomials (DKraPs) are considered a versatile family of orthogonal polynomials and are widely used in different fields such as probability theory, signal processing, digital communications, and image processing. Various recurrence algorithms have been proposed so far to address the challenge of numerical instability for large values of orders and signal sizes. The computation of DKraP coefficients was typically computed using sequential algorithms, which are computationally extensive for large order values and polynomial sizes. To this end, this paper introduces a computationally efficient solution that utilizes the parallel processing capabilities of modern central processing units (CPUs), namely the availability of multiple cores and multithreading. The proposed multi-threaded implementations for computing DKraP coefficients divide the computations into multiple independent tasks, which are executed concurrently by different threads distributed among the independent cores. This multi-threaded approach has been evaluated across a range of DKraP sizes and various values of polynomial parameters. The results show that the proposed method achieves a significant reduction in computation time. In addition, the proposed method has the added benefit of applying to larger polynomial sizes and a wider range of Krawtchouk polynomial parameters. Furthermore, an accurate and appropriate selection scheme of the recurrence algorithm is introduced. The proposed approach introduced in this paper makes the DKraP coefficient computation an attractive solution for a variety of applications.
Mitigating Large Language Model Bias: Automated Dataset Augmentation and Prejudice Quantification
Authors: Mondal Devam , Lipizzi Carlo
Published: June 2024

Despite the growing capabilities of large language models, concerns exist about the biases they develop. In this paper, we propose a novel, automated mechanism for debiasing through specified dataset augmentation in the lens of bias producers that can be useful in a variety of industries, especially ones that are “restricted” and have limited data. We consider that bias can occur due to intrinsic model architecture and dataset quality. The two aspects are evaluated using two different metrics we created. We show that our dataset augmentation algorithm reduces bias as measured by our metrics. Our code can be found on an online GitHub repository.
Observer-Based Suboptimal Controller Design for Permanent Magnet Synchronous Motors: State-Dependent Riccati Equation Controller and Impulsive Observer Approaches
Authors: Kalamian Nasrin , Soltani Masoud , Bouzari Liavoli Fariba , Faraji Niri Mona
Published: June 2024

Permanent Magnet Synchronous Motors (PMSMs) with high energy efficiency, reliable performance, and a relatively simple structure are widely utilised in various applications. In this paper, a suboptimal controller is proposed for PMSMs without sensors based on the state-dependent Riccati equation (SDRE) technique combined with customised impulsive observers (IOs). Here, the SDRE technique facilitates a pseudo-linearised display of the motor with state-dependent coefficients (SDCs) while preserving all its nonlinear features. Considering the risk of non-available/non-measurable states in the motor due to sensor and instrumentation costs, the SDRE is combined with IOs to estimate the PMSM speed and position states. Customised IOs are proven to be capable of obtaining quality, continuous estimates of the motor states despite the discrete format of the output signals. The simulation results in this work illustrate an accurate state estimation and control mechanism for the speed of the PMSM in the presence of load torque disturbances and reference speed changes. It is clearly shown that the SDRE-IO design is superior compared to the most popular existing regulators in the literature for sensorless speed control.
A Novel CNFET SRAM-Based Compute-In-Memory for BNN Considering Chirality and Nanotubes
Authors: Kim Youngbae , Alnatsheh Nader , Yadav Nandakishor , Cho Jaeik , Jo Heeyoung , Choi Kyuwon Ken
Published: June 2024

As AI models grow in complexity to enhance accuracy, supporting hardware encounters challenges such as heightened power consumption and diminished processing speed due to high throughput demands. Compute-in-memory (CIM) technology emerges as a promising solution. Furthermore, carbon nanotube field-effect transistors (CNFETs) show significant potential in bolstering CIM technology. Despite advancements in silicon semiconductor technology, CNFETs pose as formidable competitors, offering advantages in reliability, performance, and power efficiency. This is particularly pertinent given the ongoing challenges posed by the reduction in silicon feature size. We proposed an ultra-low-power architecture leveraging CNFETs for Binary Neural Networks (BNNs), featuring an advanced state-of-the-art 8T SRAM bit cell and CNFET model to optimize performance in intricate AI computations. Through meticulous optimization, we fine-tune the CNFET model by adjusting tube counts and chiral vectors, as well as optimizing transistor ratios for SRAM transistors and nanotube diameters. SPICE simulation in 32 nm CNFET technology facilitates the determination of optimal transistor ratios and chiral vectors across various nanotube diameters under a 0.9 V supply voltage. Comparative analysis with conventional FinFET-based CIM structures underscores the superior performance of our CNFET SRAM-based CIM design, boasting a 99% reduction in power consumption and a 91.2% decrease in delay compared to state-of-the-art designs.
Continuous Time Simulation and System-Level Model of a MVDC Distribution Grid Including SST and MMC-Based AFE
Authors: Siemaszko Daniel , Carpita Mauro
Published: June 2024

Medium-voltage DC (MVDC) technology has gained increasing attention in recent years. Power electronics devices dominate these grids. Accurate simulation of such a grid, with detailed models of switching semiconductors, can quickly became very time-consuming, according to the number of connected devices to be simulated. A simulation approach based on interactions on a continuous time model can be very interesting, especially for developing a system-level control model of such a modern MVDC distribution grid. The aim of this paper is to present all the steps required for obtaining a continuous time modelling of a +/−10 kV MVDC grid case study, including a solid-state transformer (SST)- and modular multilevel converter (MMC)-based active front end (AFE). An additional aim of this paper is to supply educational content about the use of the continuous time simulation approach, thanks to a detailed description of the various devices modelled into the presented MVDC grid. The results of a certain number of simulation scenarios are eventually presented.
A Case Study on Electric Vehicles as Nationwide Battery Storage to Meet Slovenia’s Final Energy Consumption with Solar Energy
Authors: Mendek Igor , Marentič Tim , Anžur Klara , Zajc Matej
Published: June 2024

Despite the global importance of solar energy, its variability requires energy storage to balance production during peak and off-peak periods. Moreover, the transport sector is undergoing a global transition from internal combustion engines to electric vehicles. Since vehicles are idle 95% of the time, electric vehicle batteries, when connected to a grid, can effectively regulate intermittent photovoltaics using vehicle-to-grid technology. This conceptual study investigates the feasibility of a nationwide energy infrastructure that relies solely on solar energy, replacing other electricity sources, such as solid fuels, petroleum products, and natural gas, and utilizes electric vehicles as the sole battery energy storage system. This study aims to demonstrate the significant potential and benefits of such collaboration. The theoretical study combines historical data, assumptions, and conditions to build a simulation model that is modelled similarly as in previous conceptual studies of nationwide energy systems based solely on photovoltaics and electric vehicles, referenced in this article. In Slovenia, the total surface size suitable for the installation of photovoltaic systems is estimated to be 280 km2. The calculations show that a surface size of 217 km2 for photovoltaic systems can produce enough energy to cover Slovenia’s entire energy demand, Slovenia’s final energy consumption. However, simulations comparing photovoltaic production, total energy consumption (electricity, solid fuels, etc.), and the capacity of electric vehicle batteries show that a surface size of more than 500 km2 with photovoltaic systems and a 200% share of electric vehicles in the Slovenian vehicle fleet in 2022 will provide satisfactory results. Therefore, for a country like Slovenia, in addition to a solar power plant with a surface size of 280 km2, additional renewable energy sources are needed to cover the total energy demand, as well as additional battery energy storage systems in addition to electric vehicles.
Experimental Study on Performance of a Wave Energy Converter Rotor with a Moving Platform
Authors: Ha Yoon-Jin , Lim Chang-Hyuck , Shin Seung-Ho , Park Ji-Yong
Published: June 2024

A series of experiments were carried out to investigate the performance of a WEC rotor with platform motion. To achieve platform motion, a forced motion device with a rotor was installed in the Ocean Engineering Basin. In this study, the rotor’s performance was examined at various phase stages between incoming waves at three wave heights, and compared to a rotor without a PTO system. The phase stage where the rotor exhibited the largest pitch motion was identified, and the efficiencies of the rotor with the PTO system were analyzed during this stage. Without the PTO system, the rotor experienced its largest pitch motion when the rotating center was positioned at the zero-up crossing point of the incoming waves at three different wave heights. Furthermore, it was observed that in the optimal phase, the rotor’s efficiency increased with relatively large platform motion. These findings provide fundamental data for rotor design.
Damage Prediction for Integrated DEAP and MRE Soft Actuators
Authors: Bernat Jakub , Kołota Jakub , Gajewski Piotr , Marcinkowska Agnieszka , Komosinski Maciej , Szczęsny Szymon
Published: June 2024

Soft robotics is a hot scientific topic in areas such as medicine and medical care, implantology, haptic technologies, and the design of various flexible structures. Integrated actuators (DEAP and MRE) are characterized by special functionality and a wider range of operations than when used individually. Such actuators can later be controlled with high voltages ranging from several to a dozen or so kV. Unfortunately, the production process of integrated actuators is multi-stage and therefore more complicated. Thus, at the stage of prototyping, microscopic errors often occur that cannot be detected using simple measurement methods. The result of such errors is actuator damage at the testing stage or in subsequent application. Unfortunately, due to high voltages, actuator damage usually leads to it catching fire, which is potentially dangerous. This work presents an approach that enables the prediction of actuator damage at the testing stage. The results of modeling damaged actuators, a modified safe testing method, and a complete supervising system for testing the actuator with protection are shown. The work is also enriched with a set of data from the analyzed damage to DEAP and MRE actuators, which may prove useful in other research on the actuators of soft robotics.
A Formulation Model to Compute the Life Cycle Environmental Impact of NiZn Batteries from Cradle to Grave
Authors: Malviya Ashwani Kumar , Zarehparast Malekzadeh Mehdi , Li Jinping , Li Boyang , Santarremigia Francisco Enrique , Molero Gemma Dolores , Villalba Sanchis Ignacio , Yepes Víctor
Published: June 2024

This paper presents a comprehensive and systematic analysis of the environmental impacts (EI) produced by novel nickel-zinc battery (RNZB) technology, which is a promising alternative for energy storage applications. The paper develops mathematical models for estimating the life cycle environmental impacts of RNZB from cradle to grave, based on an extensive literature review and the ISO standards for life cycle costing and life cycle analysis. The paper uses the ReCiPe 2016 method of life cycle analysis (LCA) to calculate the EI of RNZB in terms of eighteen Midpoint impact categories and three Endpoint impact categories: damage to human health, damage to ecosystem diversity, and damage to resource availability. The paper also compares the EI of RNZB with those of other battery technologies, such as lead-acid and lithium-ion LFP and NMC. The paper applies the models and compares results with those provided by the software openLCA (version 1.11.0), showing its reliability and concluding that NiZn batteries contribute approximately 14 MJ for CED and 0.82 kg CO2 eq. for global warming per kWh of released energy, placing them between lithium-ion and lead-acid batteries. This study suggests that NiZn battery technology could benefit from using more renewable energy in end-use applications and adopting green recovery technology to reduce environmental impact. Further developments can use these models as objective functions for heuristic optimisation of the EI in the life cycle of RNZB.
Performance Evaluation of Air-Based Photovoltaic Thermal Collector Integrated with Dual Duct and Semicircular Turbulator in Actual Climate Conditions
Authors: An Byeong-Hwa , Kim Seong-Bhin , Choi Hwi-Ung , Choi Kwang-Hwan
Published: June 2024

An air-based photovoltaic thermal collector (PVTC) is a system that generates both electricity and heat using air flowing over a photovoltaic (PV) module. This system offers the advantage of easy maintenance; however, it suffers from lower thermal efficiency compared to other PVTCs, mostly owing to the low heat capacity of air. Thus, this study introduces a novel PVTC incorporating dual ducts and semicircular turbulators, which were experimentally evaluated under actual weather conditions in the Republic of Korea. The proposed PVTC was compared with two other types of PVTC: one is a single-duct PVTC with semicircular turbulators, and the other is a dual-duct PVTC without turbulators. The results showed that the thermal efficiency of the proposed PVTC increased by approximately 88.7% compared to the single-duct PVTC with a turbulator and by 9.3% compared to the dual-duct PVTC without a turbulator. The electrical efficiency showed a slight decrease of about 7.2% compared to the single-duct PVTC but an increase of 1.4% compared to the dual-duct PVTC without a turbulator. Overall, the total efficiency of the proposed PVTC increased by 54.2% and 7.7% compared to the single-duct PVTC and the dual-duct PVTC without a turbulator, respectively. These experimental results demonstrate that attaching dual ducts and semicircular turbulators to an existing PVTC increases the daily thermal energy output, which ultimately enhances the total daily energy output.
Modeling of Electrochemical Impedance of Fuel Cell Based on Novel Nanocomposite Membrane
Authors: Zhyhailo Mariia , Yevchuk Iryna , Ivashchyshyn Fedir , Demchyna Oksana , Chabecki Piotr , Babkina Natalia , Shantaliy Tetiana
Published: June 2024

The new hybrid composite materials for PEM fuel cell were synthesized by the UV polymerization of acrylic monomers (acrylonitrile, acrylic acid, ethylene glycol dimethacrylate) and a sulfo aromatic monomer, i.e., sodium styrene sulfonate, and the tetraethoxysilane/3-methacryloxypropyltrimethoxysilane-based sol–gel system. By means of X-ray spectroscopy, the fractal structure of the obtained materials was characterized. Proton conductivity and viscoelasticity of the obtained materials were determined depending on the content of the inorganic component in nanocomposites. Based on impedance studies, an equivalent scheme is proposed that successfully describes the proton conductivity in the synthesized composite’s electrolyte membranes.
The Impact of Physicochemical Conditions on Lactic Acid Bacteria Survival in Food Products
Authors: Sionek Barbara , Szydłowska Aleksandra , Trząskowska Monika , Kołożyn-Krajewska Danuta
Published: June 2024

Lactic acid bacteria (LAB), due to their many advantageous features, have been utilized in food manufacturing for centuries. Spontaneous fermentation, in which LAB play a fundamental role, is one of the oldest methods of food preservation. LAB survival and viability in various food products are of great importance. During technological processes, external physicochemical stressors appear often in combinations. To ensure the survival of LAB, adjustment of optimal physicochemical conditions should be considered. LAB strains should be carefully selected for particular food matrices and the technological processes involved. The LAB’s robustness to different environmental stressors includes different defense mechanisms against stress, including the phenomenon of adaptation, and cross-protection. Recently established positive health effects and influence on human wellbeing have caused LAB to be some of the most desirable microorganisms in the food industry. A good understanding of LAB defense and adaptation mechanisms can lead to both optimization of food production and storage conditions, as well as to obtaining LAB strains with increased tolerance to stressors. Hopefully, as a result, the final food product with naturally present or added LAB can achieve outstanding quality and safety with health benefits that meet consumer expectations.
Fractional Lévy Stable Motion from a Segmentation Perspective
Authors: Stanislavsky Aleksander A. , Weron Aleksander
Published: June 2024

The segmentation analysis of the Golding–Cox mRNA dataset clarifies the description of these trajectories as a Fractional Lévy Stable Motion (FLSM). The FLSM method has several important advantages. Using only a few parameters, it allows for the detection of jumps in segmented trajectories with non-Gaussian confined parts. The value of each parameter indicates the contribution of confined segments. Non-Gaussian features in mRNA trajectories are attributed to trajectory segmentation. Each segment can be in one of the following diffusion modes: free diffusion, confined motion, and immobility. When free diffusion segments alternate with confined or immobile segments, the mean square displacement of the segmented trajectory resembles subdiffusion. Confined segments have both Gaussian (normal) and non-Gaussian statistics. If random trajectories are estimated as FLSM, they can exhibit either subdiffusion or Lévy diffusion. This approach can be useful for analyzing empirical data with non-Gaussian behavior, and statistical classification of diffusion trajectories helps reveal anomalous dynamics.
Derivation of Contour Plots for the Characterization of the Behaviour of Sand under Undrained Loading
Authors: Saathoff Jann-Eike , Achmus Martin
Published: June 2024

The soil response under the inherent cyclic loading conditions when dealing with offshore foundations can be considered by using contour plots. These plots are derived from several cyclic laboratory tests and characterize the general cyclic soil behaviour. In the design process with explicit numerical methods, such plots are needed in order to assess the soil behaviour under arbitrary loading conditions and hence estimate the cyclic foundation response. In the paper, excess pore pressure contour plots for a poorly graded medium sand are derived from numerous constant volume (CV) cyclic direct simple shear (DSS) tests and a new approach for parametrization of the plots is presented. Subsequently, the data are assessed regarding scaling for other sand soils, i.e., construction of contour plots with only a small number of test results by using the general trends observed.
Basic Conditions for Support of Young Carers in School: A Secondary Analysis of the Perspectives of Young Carers, Parents, Teachers, and Counselors
Authors: Kaiser Steffen , Siegemund-Johannsen Steffen , Schulze Gisela C. , Spittel Anna-Maria
Published: June 2024

Young carers face a variety of challenges at school. While schools can be vital places of support, the assistance they receive at school often seems selective and fails to consider the unique life situations of individual students. This paper examines the perspective of multiple actors in the student’s school environment and explores how schools can develop comprehensive, sustainable support systems for young carers—systems that consider and involve as many actors as possible in the student’s school environment. In a secondary analysis of two interview studies, we analyzed how young carers as well as their parents, teachers, and school counsellors perceived the school support the carers received. We then developed an integrated model that incorporates these differing perspectives. The model offers an approach for implementing low-threshold support for young carers within existing school structures in relation to their family situation and outlines conditions that can support both recognized and “invisible” young carers, as well as other students.
The Return of the Warrior: Combining Anthropology, Imaging Advances, and Art in Reconstructing the Face of the Early Medieval Skeleton
Authors: Curić Ana , Jerković Ivan , Cavalli Fabio , Kružić Ivana , Bareša Tina , Bašić Andrej , Mladineo Marko , Jozić Robert , Balić Goran , Matetić Duje , Tojčić Deni , Dolić Krešimir , Skejić Ivan , Bašić Željana
Published: June 2024

Reconstructing the face from the skull is important not only for forensic identification but also as a tool that can provide insight into the appearance of individuals from past populations. It requires a multidisciplinary approach that combines anthropological knowledge, advanced imaging methods, and artistic skills. In the present study, we demonstrate this process on the skull of an early medieval warrior from Croatia. The skeletal remains were prepared and scanned using multi-slice computed tomography (MSCT) and examined using standard anthropological and radiological methods. The analysis revealed that the remains belonged to a 35–45-year-old male individual who had suffered severe cranial trauma, probably causing his death. From MSCT images, we reconstructed a three-dimensional (3D) model of the skull, on which we digitally positioned cylinders demarking the soft tissue thickness and created the face with a realistic texture. A 3D model of the face was then optimized, printed, and used to produce a clay model. Sculpturing techniques added skin textures and facial features with scars and trauma manifestations. Finally, after constructing a plaster model, the model was painted and refined by adding fine details like eyes and hair, and it was prepared for presentation in the form of a sculpture.
Immune Response to Respiratory Viral Infections
Authors: Gambadauro Antonella , Galletta Francesca , Li Pomi Alessandra , Manti Sara , Piedimonte Giovanni
Published: June 2024

The respiratory system is constantly exposed to viral infections that are responsible for mild to severe diseases. In this narrative review, we focalized the attention on respiratory syncytial virus (RSV), influenza virus, and severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infections, responsible for high morbidity and mortality in the last decades. We reviewed the human innate and adaptive immune responses in the airways following infection, focusing on a particular population: newborns and pregnant women. The recent Coronavirus disease-2019 (COVID-19) pandemic has highlighted how our interest in viral pathologies must not decrease. Furthermore, we must increase our knowledge of infection mechanisms to improve our future defense strategies.
Apolipoproteins and Lipoproteins in Health and Disease 2.0
Authors: Rotllan Noemi , Escolà-Gil Joan Carles
Published: June 2024

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, accounting for 32% of global deaths, according to the World Health Organization (WHO) [...]
Loss of CFTR Reverses Senescence Hallmarks in SARS-CoV-2 Infected Bronchial Epithelial Cells
Authors: Merigo Flavia , Lagni Anna , Boschi Federico , Bernardi Paolo , Conti Anita , Plebani Roberto , Romano Mario , Sorio Claudio , Lotti Virginia , Sbarbati Andrea
Published: June 2024

SARS-CoV-2 infection has been recently shown to induce cellular senescence in vivo. A senescence-like phenotype has been reported in cystic fibrosis (CF) cellular models. Since the previously published data highlighted a low impact of SARS-CoV-2 on CFTR-defective cells, here we aimed to investigate the senescence hallmarks in SARS-CoV-2 infection in the context of a loss of CFTR expression/function. We infected WT and CFTR KO 16HBE14o-cells with SARS-CoV-2 and analyzed both the p21 and Ki67 expression using immunohistochemistry and viral and p21 gene expression using real-time PCR. Prior to SARS-CoV-2 infection, CFTR KO cells displayed a higher p21 and lower Ki67 expression than WT cells. We detected lipid accumulation in CFTR KO cells, identified as lipolysosomes and residual bodies at the subcellular/ultrastructure level. After SARS-CoV-2 infection, the situation reversed, with low p21 and high Ki67 expression, as well as reduced viral gene expression in CFTR KO cells. Thus, the activation of cellular senescence pathways in CFTR-defective cells was reversed by SARS-CoV-2 infection while they were activated in CFTR WT cells. These data uncover a different response of CF and non-CF bronchial epithelial cell models to SARS-CoV-2 infection and contribute to uncovering the molecular mechanisms behind the reduced clinical impact of COVID-19 in CF patients.
TumFlow: An AI Model for Predicting New Anticancer Molecules
Authors: Rigoni Davide , Yaddehige Sachithra , Bianchi Nicoletta , Sperduti Alessandro , Moro Stefano , Taccioli Cristian
Published: June 2024

Melanoma is the fifth most common cancer in the United States. Conventional drug discovery methods are inherently time-consuming and costly, which imposes significant limitations. However, the advent of Artificial Intelligence (AI) has opened up new possibilities for simulating and evaluating numerous drug candidates, thereby mitigating the requisite time and resources. In this context, normalizing flow models by employing machine learning techniques to create new molecular structures holds promise for accelerating the discovery of effective anticancer therapies. This manuscript introduces TumFlow, a novel AI model designed to generate new molecular entities with potential therapeutic value in cancer treatment. It has been trained on the NCI-60 dataset, encompassing thousands of molecules tested across 60 tumour cell lines, with an emphasis on the melanoma SK-MEL-28 cell line. The model successfully generated new molecules with predicted improved efficacy in inhibiting tumour growth while being synthetically feasible. This represents a significant advancement over conventional generative models, which often produce molecules that are challenging or impossible to synthesize. Furthermore, TumFlow has also been utilized to optimize molecules known for their efficacy in clinical melanoma treatments. This led to the creation of novel molecules with a predicted enhanced likelihood of effectiveness against melanoma, currently undocumented on PubChem.
Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications
Authors: Guerricchio Laura , Barile Lucio , Bollini Sveva
Published: June 2024

Cardiovascular disease represents the foremost cause of mortality and morbidity worldwide, with a steadily increasing incidence due to the growth of the ageing population. Cardiac dysfunction leading to heart failure may arise from acute myocardial infarction (MI) as well as inflammatory- and cancer-related chronic cardiomyopathy. Despite pharmacological progress, effective cardiac repair represents an unmet clinical need, with heart transplantation being the only option for end-stage heart failure. The functional profiling of the biological activity of extracellular vesicles (EVs) has recently attracted increasing interest in the field of translational research for cardiac regenerative medicine. The cardioprotective and cardioactive potential of human progenitor stem/cell-derived EVs has been reported in several preclinical studies, and EVs have been suggested as promising paracrine therapy candidates for future clinical translation. Nevertheless, some compelling aspects must be properly addressed, including optimizing delivery strategies to meet patient needs and enhancing targeting specificity to the cardiac tissue. Therefore, in this review, we will discuss the most relevant aspects of the therapeutic potential of EVs released by human progenitors for cardiovascular disease, with a specific focus on the strategies that have been recently implemented to improve myocardial targeting and administration routes.
Current Novel Targeted Therapeutic Strategies in Multiple Myeloma
Authors: Lin Cindy Hsin-Ti , Tariq Muhammad Junaid , Ullah Fauzia , Sannareddy Aishwarya , Khalid Farhan , Abbas Hasan , Bader Abbas , Samaras Christy , Valent Jason , Khouri Jack , Anwer Faiz , Raza Shahzad , Dima Danai
Published: June 2024

Multiple myeloma (MM) is a hematologic malignancy caused by the clonal expansion of immunoglobulin-producing plasma cells in the bone marrow and/or extramedullary sites. Common manifestations of MM include anemia, renal dysfunction, infection, bone pain, hypercalcemia, and fatigue. Despite numerous recent advancements in the MM treatment paradigm, current therapies demonstrate limited long-term effectiveness and eventual disease relapse remains exceedingly common. Myeloma cells often develop drug resistance through clonal evolution and alterations of cellular signaling pathways. Therefore, continued research of new targets in MM is crucial to circumvent cumulative drug resistance, overcome treatment-limiting toxicities, and improve outcomes in this incurable disease. This article provides a comprehensive overview of the landscape of novel treatments and emerging therapies for MM grouped by molecular target. Molecular targets outlined include BCMA, GPRC5D, FcRH5, CD38, SLAMF7, BCL-2, kinesin spindle protein, protein disulfide isomerase 1, peptidylprolyl isomerase A, Sec61 translocon, and cyclin-dependent kinase 6. Immunomodulatory drugs, NK cell therapy, and proteolysis-targeting chimera are described as well.
CaMKIV-Mediated Phosphorylation Inactivates Freud-1/CC2D1A Repression for Calcium-Dependent 5-HT1A Receptor Gene Induction
Authors: Galaraga Kimberly , Rogaeva Anastasia , Biniam Nathan , Daigle Mireille , Albert Paul R.
Published: June 2024

Calcium calmodulin-dependent protein kinase (CaMK) mediates calcium-induced neural gene activation. CaMK also inhibits the non-syndromic intellectual disability gene, Freud-1/CC2D1A, a transcriptional repressor of human serotonin-1A (5-HT1A) and dopamine-D2 receptor genes. The altered expression of these Freud-1-regulated genes is implicated in mental illnesses such as major depression and schizophrenia. We hypothesized that Freud-1 is blocked by CaMK-induced phosphorylation. The incubation of purified Freud-1 with either CaMKIIα or CaMKIV increased Freud-1 phosphorylation that was partly prevented in Freud-1-Ser644Ala and Freud-1-Thr780Ala CaMK site mutants. In human SK-N-SH neuroblastoma cells, active CaMKIV induced the serine and threonine phosphorylation of Freud-1, and specifically increased Freud-1-Thr780 phosphorylation in transfected HEK-293 cells. The activation of purified CaMKIIα or CaMKIV reduced Freud-1 binding to its DNA element on the 5-HT1A and dopamine-D2 receptor genes. In SK-N-SH cells, active CaMKIV but not CaMKIIα blocked the Freud-1 repressor activity, while Freud-1 Ser644Ala, Thr780Ala or dual mutants were resistant to inhibition by activated CaMKIV or calcium mobilization. These results indicate that the Freud-1 repressor activity is blocked by CaMKIV-induced phosphorylation at Thr780, resulting in the up-regulation of the target genes, such as the 5-HT1A receptor gene. The CaMKIV-mediated inhibition of Freud-1 provides a novel de-repression mechanism to induce 5-HT1A receptor expression for the regulation of cognitive development, behavior and antidepressant response.
NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells
Authors: Stanisavljević Suzana , Stegnjaić Goran , Jevtić Bojan , Dimitrijević Mirjana , Miljković Đorđe , Lavrnja Irena , Nikolovski Neda
Published: June 2024

Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored. Specifically, the effects of EP on DCs obtained by GM-CSF-directed differentiation of murine bone marrow precursor cells and matured under the influence of lipopolysaccharide (LPS) were examined via immunocytochemistry and RT-PCR. EP counteracted LPS-imposed morphological changes and down-regulated the LPS-induced expression of pro-inflammatory mediators in DCs. While it reduced the activation of NF-κB, EP potentiated NRF2 and downstream antioxidative molecules, thus implying the regulation of NRF2 signaling pathways as the major reason for the tolerizing effects of EP on DCs.
Molecular Force Sensors for Biological Application
Authors: Chen Huiyan , Wang Shouhan , Cao Yi , Lei Hai
Published: June 2024

The mechanical forces exerted by cells on their surrounding microenvironment are known as cellular traction forces. These forces play crucial roles in various biological processes, such as tissue development, wound healing and cell functions. However, it is hard for traditional techniques to measure cellular traction forces accurately because their magnitude (from pN to nN) and the length scales over which they occur (from nm to μm) are extremely small. In order to fully understand mechanotransduction, highly sensitive tools for measuring cellular forces are needed. Current powerful techniques for measuring traction forces include traction force microscopy (TFM) and fluorescent molecular force sensors (FMFS). In this review, we elucidate the force imaging principles of TFM and FMFS. Then we highlight the application of FMFS in a variety of biological processes and offer our perspectives and insights into the potential applications of FMFS.
Control on Flow Separation over a Cylinder by a Ferrofluid Film Adsorbed by a Magnet
Authors: Wei Chunyun , Xie Hongjia , Liu Zixuan , Zhai Xinfeng , Zhang Hongna , Li Xiaobin
Published: June 2024

Flow separation can lead to increased resistance and vibration generation, which is a difficult problem that cannot be ignored in engineering. In this paper, we propose a method of controlling flow separation by adsorbing ferrofluid onto the surface of a magnetized cylinder, taking the common flow around a cylinder as an example. Parametric effects of the ferrofluid film, including its viscosity and thickness, on the flow behavior were investigated in terms of the vortex shedding process, velocity distribution, dominant frequency, pressure distribution, and the flow motion inside the ferrofluid film. The results indicate that the ferrofluid film can suppress the generation of flow separation and achieve effective control, which is mainly caused by wall slip and the internal movement of the ferrofluid film. Furthermore, the flow separation control effect of ferrofluid thin films with different parameters varies, with low-viscosity ferrofluid exhibiting a superior control effect.
Risk Factors and Preventive Measures for Cardiovascular Diseases
Authors: Preisner Katharina , Hetjens Svetlana
Published: June 2024

Background: Cardiovascular diseases are the most frequent cause of death worldwide. The aim of this study was to identify and demonstrate correlations between mortality data and etiological factors in EU countries. The relationships presented could thus provide a better understanding of etiological factors and possible points for interventions to prevent cardiovascular diseases. The focus was on the following diseases: hypertensive heart disease, atrial flutter/atrial fibrillation, myocardial infarction, and ischemic heart disease, as well as heart failure. Methods: The data in this study come from WHO databases. Connections between the mortality rates and the possible influencing factors were analyzed. The significant factors from the correlation analysis were simultaneously evaluated using a stepwise multiple regression analysis. Results: Analysis of hypertensive heart disease in women reveals the following factors to be significant: drug expenses, health expenses on gross domestic product, and smoking. For men, population density, first admission to a drug treatment center, and drug expenses per person emerged as important factors. Admission to drug treatment centers and length of hospitalization were significant factors for atrial fibrillation and flutter. Fine dust pollution was the most important factor in heart failure. The most important influencing factor for myocardial infarction and ischemic heart disease is nitrogen dioxide concentration. For women, the second highest value is health expenses, followed by the number of outpatient contacts per year. For men, outpatient contacts are in second place. Conclusions: Prevention measures must be taken by the government. The extent to which population density has an influence on cardiovascular diseases should be examined in more detail. In order to reduce the number of initial admissions to drug treatment centers, behavioral prevention related to drug use could be improved.
Particle Beam Therapy and Surgery as Radical Treatments for Parotid Malignancies—A Single-Center Preliminary Case Study
Authors: Katagiri Katsunori , Shiga Kiyoto , Saito Daisuke , Oikawa Shin-Ichi , Ikeda Aya , Tsuchida Kodai , Miyaguchi Jun , Kusaka Takahiro , Kusaka Iori , Ariga Hisanori , Seto Ichiro , Nakasato Tatsuhiko , Koto Masashi
Published: June 2024

Background/Objectives: Particle beam therapy (PBT) was approved in April 2018 for head and neck malignancies and has since been introduced as a radical therapy for parotid malignancies. However, its prevalence and effectiveness in relation to surgical treatment have not been investigated. Methods: In this study, we evaluated 36 patients with parotid malignancy who underwent surgery (n = 26) or PBT (n = 10) and then analyzed the annual changes in the number of patients, survival rates, and clinical factors affecting prognosis. Results: Of the ten patients who opted for PBT, two and eight patients underwent PBT before and after 2018, respectively. There was a significant difference between these two groups of patients (p = 0.04). Of the ten patients who underwent PBT, five patients were recurrent cases; meanwhile, all twenty-six patients who underwent surgery were receiving initial treatment. Only one patient in each group had local recurrence after the treatment. Conclusions: The use of PBT as a radical therapy for parotid malignancies has been increasing since 2018, and patients with recurrent tumors tended to choose PBT. The outcome of the patients who underwent PBT did not seem to be inferior compared with those of the patients who underwent surgery. The histopathological type was a crucial issue in the outcomes of patients who underwent radical therapy for parotid malignancies.
Consensus Report and Recommendations on the Management of Late-stage Internal Derangement of the Temporomandibular Joint
Authors: Monje Gil Florencio , Martínez Artal Patricia , Cuevas Queipo de Llano Alberto , Muñoz Guerra Mario , González Ballester David , López Arcas José María , López Cedrún José Luis , Gutiérrez Pérez José Luis , Martín-Granizo Rafael , del Castillo Pardo de Vera José Luis , García Medina Blas , González-García Raúl , Moreno Sánchez Manuel , Rodríguez Ekaitz Valle , Fernández Sanromán Jacinto , López Martos Ricardo , Peral Cagigal Beatriz , Redondo Alamillos Marta , Morey Mas Miguel , Salcedo Gil Carlos , Ramos Medina Benito , Valls Ontañón Adaia , Masià Gridilla Jorge , Dean Ferrer Alicia
Published: June 2024

Introduction: This report investigates late-stage internal derangement (ID) of the temporomandibular joint (TMJ) with the aim of establishing a more effective and personalized treatment protocol to improve patients’ quality of life (QoL). Material and methods: A consensus was reached among maxillofacial surgeons specializing in LSID, based on a literature research and collective expert experience following the Delphi method. Consensus was considered to be achieved when a response received at least 80% of votes. Results: Four expert groups were established, respectively, focusing on diagnosis, minimally invasive surgery (MIS), open surgery and joint replacement. A comprehensive approach to late-stage ID of the TMJ requires a consensus report. This underscores the need for a personalized treatment plan, considering the variability in clinical presentations and progression of this pathology. Our recommendations aim to optimize clinical outcomes and enhance patient QoL.
Eleven New Species of the Genus Tarzetta (Tarzettaceae, Pezizales) from Mexico
Authors: Sánchez-Flores Marcos , García-Jiménez Jesús , Raymundo Tania , Martínez-González César R. , Hernández-Del Valle Juan F. , Hernández-Muñoz Marco A. , de la Fuente Javier I. , Esqueda Martín , Ávila Ortiz Alejandrina , Valenzuela Ricardo
Published: June 2024

The genus Tarzetta is distributed mainly in temperate forests and establishes ectomycorrhizal associations with angiosperms and gymnosperms. Studies on this genus are scarce in México. A visual, morphological, and molecular (ITS-LSU) description of T. americupularis, T. cupressicola, T. davidii, T. durangensis, T. mesophila, T. mexicana, T. miquihuanensis, T. poblana, T. pseudobronca, T. texcocana, and T. victoriana was carried out in this work, associated with Abies, Quercus, and Pinus. The results of SEM showed an ornamented ascospores formation by Mexican Taxa; furthermore, the results showed that T. catinus and T. cupularis are only distributed in Europe and are not associated with any American host.