bluuebunny/crossref_metadata_2025 huggingface dataset:
Comercio electrónico y marketing digital en empresas de moda en Lima Metropolitana, Perú
Authors: Alegre-Osores Patricia Lucila
Published: January 2024

Actualmente, la tendencia de compras en línea no es ajena al rubro de la moda y requiere de estrategias efectivas para llegar al público deseado. La investigación tuvo como objetivo determinar la relación entre comercio electrónico y marketing digital de las empresas de moda en Lima Metropolitana, Perú; para ello, la metodología correspondió a una investigación aplicada, de enfoque cuantitativo, diseño no experimental, de corte transversal y de alcance descriptivo correlacional. Los hallazgos evidenciaron que el comercio electrónico tiene una relación de 0,278 con el marketing digital, coligiendo que, con la mejora de la interfaz del comercio electrónico, el marketing digital se acentúa tenuemente. Se concluyó que, existe la necesidad de fortalecer las bases del interfaz del comercio electrónico, considerando que es el pilar que proporciona los medios al marketing digital para que se puedan implementar y medir las estrategias de manera efectiva.
Las fake news sobre la COVID-19 en Latinoamérica 2020-2022. Una revisión sistemática
Authors: Castro-Paredes Ana Paula , Tomailla-Sandoval Joaquín Gabriel
Published: January 2024

Desde que la COVID-19 llegó a Latinoamérica en el 2020, los rumores y las noticias falsas se empezaron a propagar de forma indiscriminada, creando en los ciudadanos miedo e incertidumbre. El objetivo del estudio es analizar las evidencias empíricas de las fake news sobre la COVID-19 en Latinoamérica, entre los años 2020 y 2022. Se realizó una revisión sistemática a través del método PRISMA y se recogieron 12 investigaciones publicadas en las bases científicas de EBSCO y ProQuest. La investigación reveló que las fake news en cuanto a la COVID-19 destacan en el impacto negativo en la salud colectiva, la propagación de desinformación a través de emociones y su relación con la inestabilidad social y política durante la pandemia.
Quantum-Inspired Neural Network Model of Optical Illusions
Authors: Maksymov Ivan S.
Published: January 2024

Ambiguous optical illusions have been a paradigmatic object of fascination, research and inspiration in arts, psychology and video games. However, accurate computational models of perception of ambiguous figures have been elusive. In this paper, we design and train a deep neural network model to simulate human perception of the Necker cube, an ambiguous drawing with several alternating possible interpretations. Defining the weights of the neural network connection using a quantum generator of truly random numbers, in agreement with the emerging concepts of quantum artificial intelligence and quantum cognition, we reveal that the actual perceptual state of the Necker cube is a qubit-like superposition of the two fundamental perceptual states predicted by classical theories. Our results finds applications in video games and virtual reality systems employed for training of astronauts and operators of unmanned aerial vehicles. They are also useful for researchers working in the fields of machine learning and vision, psychology of perception and quantum–mechanical models of human mind and decision making.
Aircraft Upset Recovery Strategy and Pilot Assistance System Based on Reinforcement Learning
Authors: Wang Jin , Zhao Peng , Zhang Zhe , Yue Ting , Liu Hailiang , Wang Lixin
Published: January 2024

The upset state is an unexpected flight state, which is characterized by an unintentional deviation from normal operating parameters. It is difficult for the pilot to recover the aircraft from the upset state accurately and quickly. In this paper, an upset recovery strategy and pilot assistance system (PAS) based on reinforcement learning is proposed. The man–machine closed-loop system was established and the upset state, such as a high angle of attack and large attitude angle, was induced. The upset recovery problem was transformed into a sequential decision problem, and the Markov decision model of upset recovery was established by taking the deflection change of the control surface as the action. The proximal policy optimization (PPO) algorithm was selected for the strategy training. The adaptive pilot model and the reinforcement learning method proposed in this paper were used to make the aircraft recover from the upset state. Based on the correspondence between the flight state, the recovery method, and the recovery result, the aircraft upset recovery safety envelopes were formed, and the four-level upset recovery PAS with alarm warning, coordinated control, and autonomous recovery modes was constructed. The results of the digital virtual flight simulation and ground flight test show that compared with a traditional single pilot, the aircraft upset recovery strategy, the upset recovery safety envelopes, and the PAS established in this study could reduce the handling burden of the pilot and improve the success rate and effect of upset recovery. This research has certain theoretical reference values for flight safety and pilot training.
Sustainable Utilization of Humic Substances and Organic Waste in Green Agriculture
Authors: Roulia Maria
Published: January 2024

Organic wastes (OW) comprise biodegradable plant, animal, and industrial and municipal waste; billions of tons are generated annually worldwide, and they are continuously produced as a result of prosperity, the increase in population, and the escalation of anthropogenic activities [...]
Application of Electrolyzed Hydrogen Water for Management of Chronic Kidney Disease and Dialysis Treatment—Perspective View
Authors: Nakayama Masaaki , Kabayama Shigeru , Miyazaki Mariko
Published: January 2024

Chronic kidney disease (CKD), which is globally on the rise, has become an urgent challenge from the perspective of public health, given its risk factors such as end-stage renal failure, cardiovascular diseases, and infections. The pathophysiology of CKD, including dialysis patients, is deeply associated with enhanced oxidative stress in both the kidneys and the entire body. Therefore, the introduction of a safe and widely applicable antioxidant therapy is expected as a measure against CKD. Electrolyzed hydrogen water (EHW) generated through the electrolysis of water has been confirmed to possess chemical antioxidant capabilities. In Japan, devices producing this water have become popular for household drinking water. In CKD model experiments conducted to date, drinking EHW has been shown to suppress the progression of kidney damage related to hypertension. Furthermore, clinical studies have reported that systemic oxidative stress in patients undergoing dialysis treatment using EHW is suppressed, leading to a reduction in the incidence of cardiovascular complications. In the future, considering EHW as one of the comprehensive measures against CKD holds significant importance. The medical utility of EHW is believed to be substantial, and further investigation is warranted.
Natural Ventilation for Cooling Energy Saving: Typical Case of Public Building Design Optimization in Guangzhou, China
Authors: Zhang Menglong , Han Wenyang , He Yufei , Xiong Jianwu , Zhang Yin
Published: January 2024

Heating ventilation and air conditioning systems account for over one-third of building energy usage, especially for public buildings, due to large indoor heat sources and high ventilation and thermal comfort requirements compared to residential buildings. Natural ventilation shows high application potential in public buildings because of its highly efficient ventilation effect and energy-saving potential for indoor heat dissipation. In this paper, a building design is proposed for a science museum with atrium-centered natural ventilation consideration. The floor layout, building orientation, and internal structure are optimized to make full use of natural ventilation for space cooling under local climatic conditions. The natural ventilation model is established through computational fluid dynamics (CFD) for airflow evaluation under indoor and outdoor pressure differences. The preliminary results show that such an atrium-centered architectural design could facilitate an average air exchange rate over 2 h−1 via the natural ventilation effect. Moreover, indoor thermal environment simulation results indicate that the exhaust air temperature can be about 5 °C higher than the indoor air mean temperature during the daytime, resulting in about 41.2% air conditioning energy saving ratio due to the free cooling effect of natural ventilation. This work can provide guidance and references for natural ventilation optimization design in public buildings.
A New Last Mile Delivery Approach for the Hybrid Truck Multi-Drone Problem Using a Genetic Algorithm
Authors: Karaköse Ebru
Published: January 2024

In this study, the use of drones in transportation and some optimization studies carried out in the literature so far were examined. Based on these investigations, a genetic algorithm-based method has been proposed to solve the hybrid truck multi-drone problem. With the proposed algorithm, scenarios have been created using single or multiple drones and one truck for a certain number of customers to be delivered, and results have been obtained. In these scenarios, the main aim is to minimize delivery time. The results obtained have also been compared with other optimization algorithms and other results in the literature, and in addition, it has been proven that there is an inverse relationship between the number of drones and the delivery time. As a result of the comparisons, it has been clearly seen that the proposed algorithm is quite successful in finding the most suitable route in the shortest time compared to other studies. A solution has been created for a real-world problem with the proposed genetic algorithm-based algorithm, and it has been concluded that it is quite successful here as well.
High-Speed Cell Assembly with Piezo-Driven Two-Finger Microhand
Authors: Zhao Yue , Deng Yan , Chen Junnan , Kojima Masaru , Huang Qiang , Arai Tatsuo , Liu Xiaoming
Published: January 2024

In the past few decades, researchers have conducted extensive studies on cell micromanipulation methods. However, there has consistently been a lack of a micromanipulation system that excels in both precision and speed. Additionally, many of these methods rely on manual control, thus significantly reducing efficiency. In this paper, a robotized micromanipulation system employing a two-finger microhand is proposed. The microhand has a 3-DoF parallel mechanism driven by three piezoelectric actuators, enabling high-precision micromanipulation. Replacing the needle-tip end-effector with a hemispherical end-effector makes cell grasping easier and more stable. In addition, a vibration-based release method combined with gel coating is proposed to reduce the release difficulty caused by adhesion forces. Through multiple sets of experiments, we have determined the optimal grasping and releasing conditions while balancing precision, stability, and damage degree to cells. An automated cell assembly strategy based on microscopic visual feedback and pick-and-place path planning is proposed to achieve the robotized high-speed cell array. Hela cells were chosen as the operation objects, achieving a 95% success rate in grasping and a 97% success rate in releasing. A “T” letter array formed by cells was successfully assembled with an average grasp and release time of less than 0.8 s and an assembly accuracy of 4.5 μm for a single cell. This study holds significant implications for the fields of biology and medicine, presenting potential applications in tissue engineering.
Monte Carlo Sampling of Inverse Problems Based on a Squeeze-and-Excitation Convolutional Neural Network Applied to Ground-Penetrating Radar Crosshole Traveltime: A Numerical Simulation Study
Authors: Qiao Hanqing , Liu Cai , Wang Shengchao
Published: January 2024

Monte Carlo-based sampling methods (MCMC) can be used to solve inverse problems affecting ground penetrating radar (GPR) data. However, due to their high computational complexity, they have not been widely used in practical applications. This article uses neural network methods to replace the computationally complex forward problem of Monte Carlo methods. However, the neural network method is an approximation of the accurate formula method, and this may introduce model errors. In order to reduce the impact of model errors, in this study, we incorporate the Squeeze-and-Excitation (SE) attention mechanism into Convolutional Neural Networks (CNN) to further improve the accuracy of the network. Moreover, with the statistical advantages of the MCMC method, model errors can be explained during the inversion process, further reducing their impact. We apply the proposed method to solve the inversion problem of crosshole ground-penetrating radar travel time data. Compared with commonly used approximate forward models, the method proposed in this paper has better accuracy. The results of data experiments indicate that this method can effectively invert the velocity of underground media.
A Study on the UWB-Based Position Estimation Method Using Dead Reckoning Information for Active Driving in a Mapless Environment of Intelligent Wheelchairs
Authors: Jang Eunsu , Eom Su-Hong , Lee Eung-Hyuk
Published: January 2024

As the world enters an aging and super-aged society, the application of advanced technology in assistive devices to support the daily life of the elderly is becoming a hot issue. Among them, electric wheelchairs are representative assistive devices for the walking support of the elderly, and their structural form is similar to AGV and AMR. For this reason, research is being introduced and underway to guarantee the right to voluntarily move or improve the convenience of movement for the elderly and severely disabled people who have difficulties in operating a joystick for operating an electric wheelchair. Autonomous driving of mobile robots is a technology that configures prior information on the driving environment as a map DB and operates based on it. However, active driving assistance technology is needed because wheelchairs do not move in a limited space, but can move to a place without a prior map DB or vehicle boarding depending on the passenger’s intention to move. Therefore, a system for estimating the moving position and direction of the wheelchair is needed to develop a driving assistance technology in the relevant driving environment. In order to solve the above problem, this study proposes a position and direction estimation algorithm suitable for active driving of a wheelchair based on a UWB sensor. This proposal is an algorithm for estimating the position and direction of the wheelchair through the fusion of UWB, IMU, and encoder sensors. In this proposal, it is difficult to design an active driving assistance system for wheelchairs due to low accuracy, obstacles, and errors due to signal strength in the position and direction estimation with UWB sensors alone. Therefore, this study proposes a wheelchair driving position and direction estimation system that fuses the dead recording information of a wheelchair and the UWB-based position estimation technique based on sensors applied in IMU and encoders. Applying quantitative verification to the proposed technique, the direction estimation accuracy of the wheelchair of about 15.3° and the position estimation error average of ±15 cm were confirmed, and it was verified that a driving guide for active driving was possible when the sensor system proposed in a mapless environment of the wheelchair was installed at a specific destination.
Towards a Timepix3 Radiation Monitor for the Accelerator Mixed Radiation Field: Characterisation with Protons and Alphas from 0.6 MeV to 5.6 MeV
Authors: Prelipcean Daniel , Lerner Giuseppe , Slipukhin Ivan , Lucsanyi David , Sandberg Hampus , Storey James , Martin-Holgado Pedro , Romero-Maestre Amor , Morilla García Yolanda , García Alía Rubén
Published: January 2024

A Timepix3 detector with a 300 μm silicon sensor has been studied as a novel radiation monitor for the mixed radiation field at the Large Hadron Collider at CERN. This work describes a test campaign carried out at Centro Nacional de Aceleradores with quasi-mono energetic protons (alphas) from 0.6 (1) to 5 (5.6) MeV, where orthogonal irradiations are used to obtain an energy calibration, and a low-energy angular scan to estimate the front dead layer thickness of the sensor. The detector is operated in hole collection mode and at a partial bias of 250 μm at 50 V, which increases the charge sharing among pixels to mitigate the signal saturation at high energy depositions. The data, supported by FLUKA Monte Carlo simulations of energy losses in the sensor, show that the Timepix3 monitor operates in a linear regime up to energy depositions of around 600 keV per pixel and 2 MeV per cluster. As a result, the detector has been found to be suitable for measuring charged particle fluxes in the LHC mixed radiation field within the linear calibration regime, with the partial exception of inelastic nuclear reaction hits (mostly from neutrons).
Research on a Mongolian Text to Speech Model Based on Ghost and ILPCnet
Authors: Ren Qing-Dao-Er-Ji , Wang Lele , Zhang Wenjing , Li Leixiao
Published: January 2024

The core challenge of speech synthesis technology is how to convert text information into an audible audio form to meet the needs of users. In recent years, the quality of speech synthesis based on end-to-end speech synthesis models has been significantly improved. However, due to the characteristics of the Mongolian language and the lack of an audio corpus, the Mongolian speech synthesis model has achieved few results, and there are still some problems with the performance and synthesis quality. First, the phoneme information of Mongolian was further improved and a Bang-based pre-training model was constructed to reduce the error rate of Mongolian phonetic synthesized words. Second, a Mongolian speech synthesis model based on Ghost and ILPCnet was proposed, named the Ghost-ILPCnet model, which was improved based on the Para-WaveNet acoustic model, replacing ordinary convolution blocks with stacked Ghost modules to generate Mongolian acoustic features in parallel and improve the speed of speech generation. At the same time, the improved vocoder ILPCnet had a high synthesis quality and low complexity compared to other vocoders. Finally, a large number of data experiments were conducted on the proposed model to verify its effectiveness. The experimental results show that the Ghost-ILPCnet model has a simple structure, fewer model generation parameters, fewer hardware requirements, and can be trained in parallel. The average subjective opinion score of its synthesized speech reached 4.48 and the real-time rate reached 0.0041. It ensures the naturalness and clarity of synthesized speech, speeds up the synthesis speed, and effectively improves the performance of the Mongolian speech synthesis model.
Use of Partial Least Squares Structural Equation Modeling (PLS-SEM) to Improve Plastic Waste Management
Authors: Pereira Lucas Menezes , Sanchez Rodrigues Vasco , Freires Francisco Gaudêncio Mendonça
Published: January 2024

This paper aims to propose improvements to plastic waste management performance via Partial Least Squares Structural Equation Modeling (PLS-SEM) using a survey’s structured questionnaire and hypothesis testing. The methodology has been applied to the metropolis of Salvador, Brazil’s third most populated city, although it can be used for other cities worldwide. All the indicators, constructs, and hypotheses concerning collection, sorting, and recycling came from a literature review. The dependence of the performance on efficiency, effectiveness, the municipality’s socioeconomic aspects, and the municipality’s infrastructure was evaluated, and both academic and practitioner public representatives were surveyed. Since almost double the minimum number of respondents answered the questionnaire and the PLS-SEM statistics showed that the modeling presents consistency, the discussion is relevant. The final results show that the respondents rated the volume of processing to be slightly more significant than the market maturity for the effectiveness of plastic waste management, which in turn contributes to performance. Once the positive influence of the municipality’s infrastructure on performance has also been verified, the Deposit-Return Systems (DRSs) should be considered for improvement, in addition to an increase in the availability of selective collection systems, contributing to the growth of both the recycling rate and business profitability, reflections of performance.
A Rotating Object Detector with Convolutional Dynamic Adaptive Matching
Authors: Yu Leibo , Zhou Yu , Li Xianglong , Hu Shiquan , Jing Dongling
Published: January 2024

Standard convolution sliding along a fixed direction in common convolutional neural networks (CNNs) is inconsistent with the direction of aerial targets, making it difficult to effectively extract features with high-aspect-ratio and arbitrary directional targets. To this end, We have fully considered the dynamic adaptability of remote sensing (RS) detectors in feature extraction and the balance of sample gradients during training and designed a plug-and-play dynamic rotation convolution with an adaptive alignment function. Specifically, we design dynamic convolutions in the backbone network that can be closely coupled with the spatial features of aerial targets. We design a network that can capture the rotation angle of aerial targets and dynamically adjust the spatial sampling position of the convolution to reduce the difference between the convolution and the target in directional space. In order to improve the stability of the network, a gradient adaptive equalization loss function is designed during training. The loss function we designed strengthens the gradient of high-quality samples, dynamically balancing the gradients of samples of different qualities to achieve stable training of the network. Sufficient experiments were conducted on the DOTA, HRSC-2016, and UCAS-AOD datasets to demonstrate the effectiveness of the proposed method and to achieve an effective balance between complexity and accuracy.
High-Noise Grayscale Image Denoising Using an Improved Median Filter for the Adaptive Selection of a Threshold
Authors: Cao Ning , Liu Yupu
Published: January 2024

Grayscale image processing is a key research area in the field of computer vision and image analysis, where image quality and visualization effects may be seriously damaged by high-density salt and pepper noise. A traditional median filter for noise removal may result in poor detail reservation performance under strong noise and the judgment performance of different noise characteristics has strong dependence and rather weak robustness. In order to reduce the effects of high-density salt and pepper noise on image quality when processing high-noise grayscale images, an improved two-dimensional maximum Shannon entropy median filter (TSETMF) is proposed for the adaptive selection of a threshold to enhance the filter performance while stably and effectively retaining the details of the images. The framework of the proposed improved TSETMF algorithm is designed in detail. The noise in images is filtered by means of automatically partitioning a window size, the threshold value of which is adaptively calculated using two-dimensional maximum Shannon entropy. The theoretical model is verified and analyzed through comparative experiments using three kinds of classical grayscale images. The experimental results demonstrate that the proposed improved TSETMF algorithm exhibits better processing performance than that of the traditional filter, with a higher suppression of high-density noise and denoising stability. This stronger ability while processing high-density noise is demonstrated by a higher peak signal-to-noise ratio (PSNR) of 24.97 dB with a 95% noise density located in the classical Lena grayscale image. The better denoising stability, with a noise density from 5% to 95%, is demonstrated by the minor decline in the PSNR of approximately 10.78% relative to a PSNR of 23.10 dB located in the classical Cameraman grayscale image. Furthermore, it can be advanced to promote higher noise filtering and stability for processing high-density salt and pepper noise in grayscale images.
Fire Tests of Load-Bearing, Light-Steel-Framed Wall Systems Insulated with Polyurethane Foam
Authors: Jelčić Rukavina Marija , Skejić Davor , Milovanović Bojan , Ščapec Tomislav
Published: January 2024

This paper presents the details of three fire tests conducted on light-steel-framed (LSF), load-bearing wall systems, which consist of polyurethane insulation injected into the cavities of the steel frame between two or three layers of gypsum fibreboard. To investigate the thermal and structural performance limits under standard fire conditions, observations were made during the tests, and temperatures and vertical displacements were recorded. Although combustible insulation was used, the results obtained are promising for the application of studied LSF wall systems in buildings, where fire resistance of more than 60 min is required.
Specific Features of Polynomials in Several Examples
Authors: Lipovetsky Stan
Published: January 2024

This paper considers polynomial characteristics useful for a better understanding of the behaviour of these functions. Taylor series for the polynomials are described by the items with even and odd derivatives and powered changes in the argument, which leads to more specific studying of their properties. Connections between the derivative and antiderivative of the polynomial functions are defined. The structure of polynomial functions reveals their specific characteristic that the mean value of their roots equals the mean value of the locations of the critical points such as the extrema and inflection points. Derivatives of the quadratic exponent in relation to an interesting connection of two transcendental numbers are also described. The discussed properties of the polynomials can be helpful for practical implementations and educational purposes.
Data-Driven Insights into Labor Progression with Gaussian Processes
Authors: Zhoroev Tilekbek , Hamilton Emily F. , Warrick Philip A.
Published: January 2024

Clinicians routinely perform pelvic examinations to assess the progress of labor. Clinical guidelines to interpret these examinations, using time-based models of cervical dilation, are not always followed and have not contributed to reducing cesarean-section rates. We present a novel Gaussian process model of labor progress, suitable for real-time use, that predicts cervical dilation and fetal station based on clinically relevant predictors available from the pelvic exam and cardiotocography. We show that the model is more accurate than a statistical approach using a mixed-effects model. In addition, it provides confidence estimates on the prediction, calibrated to the specific delivery. Finally, we show that predicting both dilation and station with a single Gaussian process model is more accurate than two separate models with single predictions.
The Ethylene Biosynthetic Enzymes, 1-Aminocyclopropane-1-Carboxylate (ACC) Synthase (ACS) and ACC Oxidase (ACO): The Less Explored Players in Abiotic Stress Tolerance
Authors: Khan Sheen , Alvi Ameena Fatima , Saify Sadaf , Iqbal Noushina , Khan Nafees A.
Published: January 2024

Ethylene is an essential plant hormone, critical in various physiological processes. These processes include seed germination, leaf senescence, fruit ripening, and the plant’s response to environmental stressors. Ethylene biosynthesis is tightly regulated by two key enzymes, namely 1-aminocyclopropane-1-carboxylate synthase (ACS) and 1-aminocyclopropane-1-carboxylate oxidase (ACO). Initially, the prevailing hypothesis suggested that ACS is the limiting factor in the ethylene biosynthesis pathway. Nevertheless, accumulating evidence from various studies has demonstrated that ACO, under specific circumstances, acts as the rate-limiting enzyme in ethylene production. Under normal developmental processes, ACS and ACO collaborate to maintain balanced ethylene production, ensuring proper plant growth and physiology. However, under abiotic stress conditions, such as drought, salinity, extreme temperatures, or pathogen attack, the regulation of ethylene biosynthesis becomes critical for plants’ survival. This review highlights the structural characteristics and examines the transcriptional, post-transcriptional, and post-translational regulation of ACS and ACO and their role under abiotic stress conditions. Reviews on the role of ethylene signaling in abiotic stress adaptation are available. However, a review delineating the role of ACS and ACO in abiotic stress acclimation is unavailable. Exploring how particular ACS and ACO isoforms contribute to a specific plant’s response to various abiotic stresses and understanding how they are regulated can guide the development of focused strategies. These strategies aim to enhance a plant’s ability to cope with environmental challenges more effectively.
Blood Biomarkers of Alzheimer’s Disease and Cognition: A Literature Review
Authors: Garcia-Escobar Greta , Manero Rosa Maria , Fernández-Lebrero Aida , Ois Angel , Navalpotro-Gómez Irene , Puente-Periz Victor , Contador-Muñana José , Estragués-Gazquez Isabel , Puig-Pijoan Albert , Jiménez-Balado Joan
Published: January 2024

Recent advances in blood-based biomarkers of Alzheimer’s Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations of amyloid-β (Aβ), Total Tau (t-Tau), Phosphorylated Tau (p-Tau), Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) with cognitive measures. The reviewed studies are heterogeneous, varying in design and population (cognitively unimpaired, cognitively impaired, or mixed populations), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, t-Tau, p-Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-Tau measures generally exhibit stronger associations with cognitive functions compared to other biomarkers, no single blood marker has emerged as being predominantly linked to a specific cognitive domain. These findings contribute to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical assessments of cognition.
Development of a Novel Covalently Bonded Conjugate of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) for Wound-Compatible and Injectable Hydrogel to Accelerate Healing
Authors: Baravkar Sachin B. , Lu Yan , Masoud Abdul-Razak , Zhao Qi , He Jibao , Hong Song
Published: January 2024

Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear magnetic resonance spectroscopy. Of them, 13 conjugates formed hydrogels at low concentrations (≥0.25% w/v), but C8 acid-ILD-NH2 showed the best hydrogelation and was investigated further. Scanning electron microscopy revealed that C8 acid-ILD-NH2 formed fibrous network structures and rapidly formed hydrogels that were stable in phosphate-buffered saline (pH 2–8, 37 °C), a typical pathophysiological condition. Injection and rheological studies revealed that the hydrogels manifested important wound treatment properties, including injectability, shear thinning, rapid re-gelation, and wound-compatible mechanics (e.g., moduli G″ and G′, ~0.5–15 kPa). The C8 acid-ILD-NH2(2) hydrogel markedly accelerated the healing of third-degree burn wounds on C57BL/6J mice. Taken together, our findings demonstrated the potential of the Cn fatty acid–AA1–AA2–D molecular template to form hydrogels capable of promoting the wound healing of third-degree burns.
GelMA/PEDOT:PSS Composite Conductive Hydrogel-Based Generation and Protection of Cochlear Hair Cells through Multiple Signaling Pathways
Authors: Tan Fei , Li Xuran , Li Xiao , Xu Maoxiang , Shahzad Khawar Ali , Hou Lei
Published: January 2024

Recent advances in cochlear implantology are exemplified by novel functional strategies such as bimodal electroacoustic stimulation, in which the patient has intact low-frequency hearing and profound high-frequency hearing pre-operatively. Therefore, the synergistic restoration of dysfunctional cochlear hair cells and the protection of hair cells from ototoxic insults have become a persistent target pursued for this hybrid system. In this study, we developed a composite GelMA/PEDOT:PSS conductive hydrogel that is suitable as a coating for the cochlear implant electrode for the potential local delivery of otoregenerative and otoprotective drugs. Various material characterization methods (e.g., 1H NMR spectroscopy, FT-IR, EIS, and SEM), experimental models (e.g., murine cochlear organoid and aminoglycoside-induced ototoxic HEI-OC1 cellular model), and biological analyses (e.g., confocal laser scanning microscopy, real time qPCR, flow cytometry, and bioinformatic sequencing) were used. The results demonstrated decent material properties of the hydrogel, such as mechanical (e.g., high tensile stress and Young’s modulus), electrochemical (e.g., low impedance and high conductivity), biocompatibility (e.g., satisfactory cochlear cell interaction and free of systemic toxicity), and biosafety (e.g., minimal hemolysis and cell death) features. In addition, the CDR medicinal cocktail sustainably released by the hydrogel not only promoted the expansion of the cochlear stem cells but also boosted the trans-differentiation from cochlear supporting cells into hair cells. Furthermore, hydrogel-based drug delivery protected the hair cells from oxidative stress and various forms of programmed cell death (e.g., apoptosis and ferroptosis). Finally, using large-scale sequencing, we enriched a complex network of signaling pathways that are potentially downstream to various metabolic processes and abundant metabolites. In conclusion, we present a conductive hydrogel-based local delivery of bifunctional drug cocktails, thereby serving as a potential solution to intracochlear therapy of bimodal auditory rehabilitation and diseases beyond.
Metalloproteinases as Biomarkers and Sociomarkers in Human Health and Disease
Authors: Costa Davide , Scalise Enrica , Ielapi Nicola , Bracale Umberto Marcello , Andreucci Michele , Serra Raffaele
Published: January 2024

Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients’ social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with “sociomarkers” to develop mathematical predictive models.
Clinical Significance and Expression Pattern of RIP5 and VGLL4 in Clear Cell Renal Cell Carcinoma Patients Treated with Sunitinib
Authors: Tomić Tanja , Tomić Davor , Vukoja Martina , Kraljević Marija , Ljevak Ivona , Glamočlija Una , Tomić Vajdana , Vukojević Katarina , Beljan Perak Renata , Šoljić Violeta
Published: January 2024

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5—RIP5 and Vestigial Like Family Member 4—VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.
Do the Differences in the Epiligament of the Proximal and Distal Parts of the Anterior Cruciate Ligament Explain Their Different Healing Capacities? Quantitative and Immunohistochemical Analysis of CD34 and α-SMA Expression in Relation to the Epiligament Theory
Authors: Georgiev Georgi P. , Yordanov Yordan , Olewnik Łukasz , Tubbs Richard Shane , LaPrade Robert F. , Ananiev Julian , Slavchev Svetoslav A. , Dimitrova Iva N. , Gaydarski Lyubomir , Landzhov Boycho
Published: January 2024

The aim of this study was to assess the epiligament theory by determining the normal epiligament morphology of the proximal and distal parts of the anterior cruciate ligament in humans and analyzing the differences between them and the midportion of the ligament in terms of cell numbers and expression of CD34 and α-SMA. Samples were obtained from the anterior cruciate ligaments of 12 fresh knee joints. Monoclonal antibodies against CD34 and α-SMA were used for immunohistochemistry. Photomicrographs were analyzed using ImageJ software, version 1.53f. The cell density was higher in the epiligament than in the ligament connective tissue. Cell counts were higher in the proximal and distal thirds than in the midsubstance of the epiligament. CD34 was expressed similarly in the proximal and distal thirds, although it seemed slightly more pronounced in the distal third. α-SMA expression was more robust in the proximal than the distal part. The results revealed that CD34 and α-SMA are expressed in the human epiligament. The differences between the numbers of cells in the proximal and distal parts of the epiligament and the expression of CD34 and α-SMA enhance epiligament theory. Future investigations into improving the quality of ligament healing should not overlook the epiligament theory.
Shared Genetics between Age at Menarche and Type 2 Diabetes Mellitus: Genome-Wide Genetic Correlation Study
Authors: Cheng Yuan-Fang , Yang Cheng-Yi , Tsai Meng-Che
Published: January 2024

Background: Age at menarche (AAM) has been associated with type 2 diabetes mellitus (T2DM). However, little is known about their shared heritability. Methods: Our data comes from the Taiwan Biobank. Genome-wide association studies (GWASs) were conducted to identify single-nucleotide polymorphisms (SNPs) related to AAM-, T2DM-, and T2DM-related phenotypes, such as body fat percentage (BFP), fasting blood glucose (FBG), and hemoglobin A1C (HbA1C). Further, the conditional false discovery rate (cFDR) method was applied to examine the shared genetic signals. Results: Conditioning on AAM, Quantile-quantile plots showed an earlier departure from the diagonal line among SNPs associated with BFP and FBG, indicating pleiotropic enrichments among AAM and these traits. Further, the cFDR analysis found 39 independent pleiotropic loci that may underlie the AAM-T2DM association. Among them, FN3KRP rs1046896 (cFDR = 6.84 × 10−49), CDKAL1 rs2206734 (cFDR = 6.48 × 10−10), B3GNTL1 rs58431774 (cFDR = 2.95 × 10−10), G6PC2 rs1402837 (cFDR = 1.82 × 10−8), and KCNQ1 rs60808706 (cFDR = 9.49 × 10−8) were highlighted for their significant genetic enrichment. The protein–protein interaction analysis revealed a significantly enriched network among novel discovered genes that were mostly found to be involved in the insulin and glucagon signaling pathways. Conclusions: Our study highlights potential pleiotropic effects across AAM and T2DM. This may shed light on identifying the genetic causes of T2DM.
Co-Administration of Proton Pump Inhibitors May Negatively Affect the Outcome in Inflammatory Bowel Disease Treated with Vedolizumab
Authors: Szemes Kata , Farkas Nelli , Sipos Zoltan , Bor Renata , Fabian Anna , Szepes Zoltan , Farkas Klaudia , Molnar Tamas , Schafer Eszter , Szamosi Tamas , Salamon Agnes , Vincze Aron , Sarlos Patricia
Published: January 2024

Concomitant medications may alter the effect of biological therapy in inflammatory bowel disease. The aim was to investigate the effect of proton pump inhibitors on remission rates in patients with inflammatory bowel disease treated with the gut-selective vedolizumab. Patients from the Hungarian nationwide, multicenter vedolizumab cohort were selected for post hoc analysis. Primary outcomes were the assessment of clinical response and endoscopic and clinical remission at weeks 14 and 54. Secondary outcomes were the evaluation of the combined effect of concomitant steroid therapy and other factors, such as smoking, on remission. A total of 108 patients were identified with proton pump inhibitor data from 240 patients in the original cohort. Patients on steroids without proton pump inhibitors were more likely to have a clinical response at week 14 than patients on concomitant PPI (95% vs. 67%, p = 0.005). Non-smokers with IBD treated with VDZ were more likely to develop a clinical response at week 14 than smokers, particularly those not receiving PPI compared with patients on co-administered PPI therapy (81% vs. 53%, p = 0.041, and 92% vs. 74%, p = 0.029, respectively). We found that the use of PPIs in patients treated with VDZ may impair the achievement of response in certain subgroups. Unnecessary PPI prescriptions should be avoided.
Engineering Electrode Polarity for Enhancing In Situ Generation of Hydroxyl Radicals Using Granular Activated Carbon
Authors: Sarrouf Stephanie , Taqieddin Amir , Ehsan Muhammad Fahad , Alshawabkeh Akram N.
Published: January 2024

Recently, granular activated carbon (GAC) has shown its effectiveness as a cathode material for in situ ROS generation. Here, we present an electrochemically modified GAC cathode using electrode polarity reversal (PR) approach for enhanced H2O2 decomposition via 2-electron oxygen reduction reaction (2e-ORR). The successful GAC modification using PR necessitates tuning of the operational parameters such as frequency, current, and time intervals between the PR cycles. This modification enhances the GAC hydrophilicity by increasing the density of surface oxygen functionalities. After optimization of the electrode polarity, using the 20 (No PR)-2 (PR) interval and 140 mA current intensity, the •OH concentration reaches 38.9 μM compared to the control (No PR) (28.14 μM). Subsequently, we evaluated the enhanced •OH generation for the removal of glyphosate, a persistent pesticide used as a model contaminant. The modified GAC using PR removed 67.6% of glyphosate compared to 40.6% by the unmodified GAC without PR, respectively. The findings from this study will advance the utilization of GAC for in situ ROS synthesis, which will have direct implications on increasing the effectiveness of electrochemical water treatment systems.
Cellular Strategies for Separating GvHD from GvL in Haploidentical Transplantation
Authors: Di Ianni Mauro , Liberatore Carmine , Santoro Nicole , Ranalli Paola , Guardalupi Francesco , Corradi Giulia , Villanova Ida , Di Francesco Barbara , Lattanzio Stefano , Passeri Cecilia , Lanuti Paola , Accorsi Patrizia
Published: January 2024

GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration, which are based on the use of TCR alpha/beta depletion, CD45RA depletion, T regulatory cell enrichment, NK-cell-based immunotherapies, and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.
Quality Control of Stem Cell-Based Cultured Meat According to Specific Differentiation Abilities
Authors: Naraoka Yuna , Mabuchi Yo , Kiuchi Mai , Kumagai Kyoko , Hisamatsu Daisuke , Yoneyama Yosuke , Takebe Takanori , Akazawa Chihiro
Published: January 2024

The demand for stem cell-based cultured meat as an alternative protein source is increasing in response to global food scarcity. However, the definition of quality controls, including appropriate growth factors and cell characteristics, remains incomplete. Cluster of differentiation (CD) 29 is ubiquitously expressed in bovine muscle tissue and is a marker of progenitor cells in cultured meat. However, CD29+ cells are naturally heterogeneous, and this quality control issue must be resolved. In this study, the aim was to identify the subpopulation of the CD29+ cell population with potential utility in cultured meat production. The CD29+ cell population exhibited heterogeneity, discernible through the CD44 and CD344 markers. CD29+CD44−CD344− cells displayed the ability for long-term culture, demonstrating high adipogenic potential and substantial lipid droplet accumulation, even within 3D cultures. Conversely, CD29+CD44+ cells exhibited rapid proliferation but were not viable for prolonged culture. Using cells suitable for adipocyte and muscle differentiation, we successfully designed meat buds, especially those rich in fat. Collectively, the identification and comprehension of distinct cell populations within bovine tissues contribute to quality control predictions in meat production. They also aid in establishing a stable and reliable cultured meat production technique.