bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Approach for Deepfake Detection with the Choquet Fuzzy Integral
Authors: Karaköse Mehmet , İlhan İsmail , Yetiş Hasan , Ataş Serhat
Published: August 2024

Deepfakes have become widespread and have continued to develop rapidly in recent years. In addition to the use of deepfakes in movies and for humorous purposes, this technology has also begun to pose a threat to many companies and politicians. Deepfake detection is critical to the prevention of this threat. In this study, a Choquet fuzzy integral-based deepfake detection method is proposed to increase overall performance by combining the results obtained from different deepfake detection methods. Three different deepfake detection models were used in the study: XceptionNet, which has better performance in detecting real images/videos; EfficientNet, which has better performance in detecting fake videos; and a model based on their hybrid uses. The proposed method based on the Choquet fuzzy integral aims to eliminate the shortcomings of these methods by using each of the other methods. As a result, a higher performance was achieved with the proposed method than found when all three methods were used individually. As a result of the testing and validation studies carried out on FaceForensics++, DFDC, Celeb-DF, and DeepFake-TIMIT datasets, the individual performance levels of the algorithms used were 81.34%, 82.78%, and 79.15% on average, according to the AUC curve, while the level of 97.79% was reached with the proposed method. Considering that the average performance of the three methods across all datasets is 81.09%, it can be seen that an improvement of approximately 16.7% is achieved. In the FaceForensics++ dataset, in which individual algorithms are more successful, the performance of the proposed method reaches the highest AUC value, 99.8%. It can be seen that the performance rates can be increased by changing the individual methods discussed in the proposed method. We believe that the proposed method will inspire researchers and will be further developed.
Football Analytics: Assessing the Correlation between Workload, Injury and Performance of Football Players in the English Premier League
Authors: Chang Victor , Sajeev Sreeram , Xu Qianwen Ariel , Tan Mengmeng , Wang Hai
Published: August 2024

The aim of this research is to shed light on the complex interactions between player workload, traits, match-related factors, football performance, and injuries in the English Premier League. Using a range of statistical and machine learning techniques, this study analyzed a comprehensive dataset that included variables such as player workload, personal traits, and match statistics. The dataset comprises information on 532 players across 20 football clubs for the 2020–2021 English Premier League season. Key findings suggest that data, age, average minutes played per game, and club affiliations are significant indicators of both performance and injury incidence. The most effective model for predicting performance was Ridge Regression, whereas Extreme Gradient Boosting (XGBoost) was superior for predicting injuries. These insights are invaluable for data-driven decision-making in sports science and football teams, aiding in injury prevention and performance enhancement. The study’s methodology and results have broad applications, extending beyond football to impact other areas of sports analytics and contributing to a flexible framework designed to enhance individual performance and fitness.
Utilization of the Nutritional Potential of Wheat Bran Using Different Fractionation Techniques
Authors: Skřivan Pavel , Sluková Marcela , Stýblová Barbora , Trusová Šárka , Sinica Andrej , Bleha Roman , Švec Ivan , Kotrcová Veronika
Published: August 2024

Wheat bran separated in the standard milling process as a by-product contains many substances of importance in livestock and human nutrition. In the Czech Republic, as in other Central European countries, a significant part of the bran is not traditionally used as a raw material for feed production and is used as a heating fuel. This means that many interesting and health-promoting components of fiber, phenolic compounds, vitamins, proteins, and minerals are lost. The bran is made up of particles of the grain outer coating and sub-coating layers, particularly the pericarp, testa, and aleurone layer. Their composition varies, but while the pericarp in particular is largely composed of cellulose and lignin, the testa and aleurone layer contain many valuable non-starch polysaccharides (hemicelluloses), as well as the macro- and micronutrients mentioned above. Wholemeal flours contain all the anatomical parts of the grain mentioned above, which brings both technological problems in terms of their bakery processing and a not always acceptable sensory impact on the products. This paper summarizes selected physical and physicochemical methods that can be used to remove those components that may cause technological and sensory problems and retain those that, on the other hand, represent a significant nutritional benefit.
Predicting Football Match Results Using a Poisson Regression Model
Authors: Loukas Konstantinos , Karapiperis Dimitrios , Feretzakis Georgios , Verykios Vassilios S.
Published: August 2024

Currently, several techniques based on probabilities and statistics, along with the rapid advancements in computational power, have deepened our understanding of a football match result, giving us the capability to estimate future matches’ results based on past performances. The ability to estimate the number of goals scored by each team in a football match has revolutionized the perspective of a match result for both betting market professionals and fans alike. The Poisson distribution has been widely used in a number of studies to model the number of goals a team is likely to score in a football match. Therefore, the match result can be estimated using a double Poisson regression model—one for each participating team. In this study, we propose an algorithm, which, by using Poisson distributions along with football teams’ historical performance, is able to predict future football matches’ results. This algorithm has been developed based on the Premier League’s—England’s top-flight football championship—results from the 2022–2023 season.
Detection of Arrhythmias Using Heart Rate Signals from Smartwatches
Authors: Huillcen Baca Herwin Alayn , Muñoz Del Carpio Toia Agueda , Sulla Torres José Alfredo , Cusirramos Montesinos Roderick , Contreras Salas Lucia Alejandra , Correa Herrera Sandra Catalina
Published: August 2024

According to the World Health Organization (WHO), cardiovascular illnesses, including arrhythmia, are the primary cause of mortality globally, responsible for over 31% of all fatalities each year. To reduce mortality, early and precise diagnosis is essential. Although the analysis of electrocardiograms (ECGs) is the primary means of detecting arrhythmias, it depends significantly on the expertise and subjectivity of the health professional reading and interpreting the ECG, and errors may occur in detection. Artificial intelligence provides tools, techniques, and models that can support health professionals in detecting arrhythmias. However, these tools are based only on ECG data, of which the process of obtaining is an invasive, high-cost method requiring specialized equipment and personnel. Smartwatches feature sensors that can record real-time signals indicating the heart’s behavior, such as ECG signals and heart rate. Using this approach, we propose a machine learning- and deep learning-based approach for detecting arrhythmias using heart rate data obtained with smartwatches. Heart rate data were collected from 252 patients with and without arrhythmias who attended a clinic in Arequipa, Peru. Heart rates were also collected from 25 patients who wore smartwatches. Ten machine learning algorithms were implemented to generate the most effective arrhythmia recognition model, with the decision tree algorithm being the most suitable. The results were analyzed using accuracy, sensitivity, and specificity metrics. Using Holter data yielded values of 93.2%, 91.89%, and 94.59%, respectively. Using smartwatch data yielded values of 70.83%, 91.67%, and 50%, respectively. These results indicate that our model can effectively recognize arrhythmias from heart rate data. The high sensitivity score suggests that our model adequately recognizes true positives; that is, patients with arrhythmia. Likewise, its specificity suggests an adequate recognition of false positives.
Multilevel Drought-Induced Resistance and Resilience Analysis for Vegetation in the Yellow River Basin
Authors: Fan Jingjing , Zhang Wenwei , Xu Fanfan , Zhou Xiong , Dong Wei , Wu Chenyu , Wei Shibo , Zhao Yue , Wang Dongnan
Published: August 2024

In this study, a multilevel drought-induced resistance and resilience analysis (MDRRA) approach was developed to investigate the stability of vegetation in the Yellow River Basin (YRB). MDRRA was quantified by utilizing the Normalized Difference Vegetation Index (NDVI). It was applied to YRB to assess vegetation resistance and resilience to various levels of drought by utilizing precipitation and NDVI data from 2000 to 2019. The results reveal that vegetation resistance and resilience in YRB are affected by drought severity. Monthly and annual changes in SPI over the warm–temperate humid zone of the YRB show a decreasing trend, with rates of 0.001 per decade and 0.034 per decade, respectively; however, the other climatic subregions exhibit an increasing trend, with rates ranging from 0.002 per decade to 0.82 per decade. Over 77.56% of the downstream areas show increases in the annual SPI averages. Drought severity differs across subregions in the YRB. More severe drought events occur in its upper and middle reaches, while less severe ones happen in its lower reaches. As the drought severity increases, the arid and semiarid regions of the mesothermal zone exhibit a decrease in the resistance and resilience indices. MDRRA can help improve the stability and resilience of the ecosystem in the YRB.
Indoor Concentration Distributions of Ammonia and Sulfur-Based Odorous Substances According to Types of Laying Hen Houses in South Korea
Authors: Kim Ki-Youn , Kim Jung-Kon
Published: August 2024

In South Korea, environmental complaints related to livestock odors continue to increase, and various efforts are underway to overcome them. An objective of this study is to monitor indoor concentrations of ammonia and sulfur-based odorous substances emitted from laying hen houses in South Korea through on-site visits for one year to understand their temporal emission patterns. The highest concentration was found in ammonia (NH3), at 6.92 ppmv, followed by hydrogen sulfide (H2S), at 8.98 ppbv. The concentrations of methyl mercaptan (CH3SH), dimethyl sulfide (DMS), and dimethyldisulfide (DMDS) ranged from sub ppbv to 10 ppbv. In general, there was no consistent concentration distribution of ammonia and sulfur-based odorous substances in laying hen houses between those with forced ventilation and natural ventilation. Regarding the seasonal distribution of odorous compounds, their concentrations in winter season (December to February) when the ventilation rate in laying hen houses decreased were generally higher than those in the summer season (June to August) when the ventilation rate in poultry buildings was relatively high, which is applied to properly maintain the thermal environment in laying hen houses. The limitation of this study is that unexpected conditions such as clearance of laying hen houses, chicken shipments, and disorders of exhaust fans were not controlled for intentionally due to on-site investigations.
A Laboratory Model of the Large-Scale Atmospheric Circulation of Tidally Locked Exoplanets
Authors: Vass Bálint , Kadlecsik Ádám , Vincze Miklós
Published: August 2024

We report on a novel fluid dynamics experiment configuration based on a modified version of the differentially heated rotating annulus, a widely used laboratory model of the large-scale mid-latitude atmospheric circulation. Through applying an azimuthally (zonally) inhomogeneous, dipole-like thermal boundary condition—imitating a permanent “day side” and “night side” in the rotating setting—we explore the character of the flow patterns emerging at different values of the zonal temperature contrast and rotation rate. This configuration may prove to be a useful minimal model of the large-scale atmospheric circulation of tidally locked exoplanets.
Projection of Extreme Summer Precipitation over Hubei Province in the 21st Century
Authors: Mubark Abrar , Chen Qian , Abdallah Mohamed , Hussien Awad , Hamadalnel Monzer
Published: August 2024

The link between the escalation of global warming and the increase in extreme precipitation events necessitates a deeper understanding of future trends. This study focused on the dynamics of extreme rainfall in Hubei Province throughout the 21st century, a region already sensitive to climatic shifts and extreme weather occurrences. Using the high-resolution global climate model RegCM4 driven by another high-resolution model, HadGEM2-ES, and based on the representative concentration pathway (RCP8.5) emissions scenario, this research predicted the changes in rainfall patterns in Hubei Province during the summer of the 21st century. The accuracy of the adjusted model was confirmed through the use of five extreme rainfall indices (EPIs), namely maximum 5-day amount of precipitation (RX5day), number of heavy rain days (R10), the simple daily intensity index (SDII), consecutive dry days (CDD), and consecutive wet days (CWD), that measured the intensity and frequency of such events. In particular, excluding the index for continuous dry days (CDD), there was an anticipated increase in extreme rainfall during the summer in the mid-21st century. The number of heavy rain days (R10mm) increased significantly (p < 0.05) in the southeastern parts, especially for Wuhan, Xiantao, Qianjiang, Jinzhou, and Ezhou. The EPI values were higher in southeastern Hubei. Consequently, areas such as Wuhan, Xiantao, and Qianjiang in Hubei Province are projected to face more frequent and severe extreme rainfall episodes as the century progresses.
A Novel Multi-Objective Dynamic Reliability Optimization Approach for a Planetary Gear Transmission Mechanism
Authors: Tong Shuiguang , Yan Xiaoyan , Yang Lechang , Yang Xianmiao
Published: August 2024

Planetary gear transmission mechanisms (PGTMs) are widely used in mechanical transmission systems due to their compact structure and high transmission efficiency. To implement the reliability design and optimization of a PGTM, a novel multi-objective dynamic reliability optimization approach is proposed. First, a multi-objective reliability optimization model is established. Furthermore, considering the strength degradation of gears during service, a dynamic reliability analysis is conducted based on the theory of nonlinear fatigue damage accumulation. In addition, to improve computing efficiency, a random forest surrogate model based on the particle swarm optimization algorithm is proposed. Finally, an adaptive multi-objective evolutionary algorithm based on decomposition (AMOEA/D) is designed to optimize the mechanism, along with an adaptive neighborhood updating strategy and a hybrid crossover operator. The feasibility and superiority of the proposed approach are verified through an NGW planetary gear reducer. The results show that the proposed surrogate model can reduce the calculation cost and has high accuracy. The AMOEA/D algorithm can improve transmission efficiency, reduce gear volume and ensure reliability at the same time. It can provide guidance for actual gear production.
Controlled Lateral Pressure on Cortical Bone Using Blade-Equipped Implants: An Experimental Study in Rabbits
Authors: Ferreira Balan Vitor , Ferri Mauro , Pires Godoy Eduardo , Artioli Leticia Gabriela , Botticelli Daniele , Silva Erick Ricardo , Xavier Samuel Porfirio
Published: August 2024

Background: This study aimed to evaluate the biological behavior of a novel implant design incorporating decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcomes in cortical regions where decompressive protocols were implemented using implants equipped with blades and installed applying a bicortical anchorage. Materials and Methods: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. Results: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. Conclusions: The use of a blade incorporated into the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.
Substantiation and Effectiveness of Remote Monitoring System Based on IoMT Using Portable ECG Device
Authors: Lee Hee-Young , Kim Yoon-Ji , Lee Kang-Hyun , Lee Jung-Hun , Cho Sung-Pil , Park Junghwan , Park Il-Hwan , Youk Hyun
Published: August 2024

Cardiovascular disease is a major global health concern, with early detection being critical. This study assesses the effectiveness of a portable ECG device, based on Internet of Medical Things (IoMT) technology, for remote cardiovascular monitoring during daily activities. We conducted a clinical trial involving 2000 participants who wore the HiCardi device while engaging in hiking activities. The device monitored their ECG, heart rate, respiration, and body temperature in real-time. If an abnormal signal was detected while a physician was remotely monitoring the ECG at the IoMT monitoring center, he notified the clinical research coordinator (CRC) at the empirical research site, and the CRC advised the participant to visit a hospital. Follow-up calls were made to determine compliance and outcomes. Of the 2000 participants, 318 showed abnormal signals, and 182 were advised to visit a hospital. The follow-up revealed that 139 (76.37%) responded, and 30 (21.58% of those who responded) sought further medical examination. Most visits (80.00%) occurred within one month. Diagnostic approaches included ECG (56.67%), ECG and ultrasound (20.00%), ultrasound alone (16.67%), ECG and X-ray (3.33%), and general treatment (3.33%). Seven participants (23.33% of those who visited) were diagnosed with cardiovascular disease, including conditions such as arrhythmia, atrial fibrillation, and stent requirements. The portable ECG device using the patch-type electrocardiograph detected abnormal cardiovascular signals, leading to timely diagnoses and interventions, demonstrating its potential for broad applications in preventative healthcare.
The Potential of Composite Cements for Wound Healing in Rats
Authors: Ardelean Alina Ioana , Marza Sorin Marian , Dragomir Madalina Florina , Negoescu Andrada , Sarosi Codruta , Novac Cristiana Stefania , Pestean Cosmin , Moldovan Marioara , Oana Liviu
Published: August 2024

Recent developments in biomaterials have resulted in the creation of cement composites with potential wound treatment properties, even though they are currently mainly employed for bone regeneration. Their ability to improve skin restoration after surgery is worth noting. The main purpose of this research is to evaluate the ability of composite cement to promote wound healing in a rat experimental model. Full-thickness 5 mm skin defects were created, and the biomaterials were applied as wound dressings. The hybrid light-cured cement composites possess an organic matrix (Bis-GMA, TEGDMA, UDMA, and HEMA) and an inorganic phase (bioglasses, silica, and hydroxyapatite). The organic phase also contains γ-methacryloxypropyl-trimethoxysilane, which is produced by distributing bioactive silanized inorganic filler particles. The repair of the defect is assessed using a selection of macroscopic and microscopic protocols, including wound closure rate, histopathological analysis, cytotoxicity, and biocompatibility. Both composites exerted a favorable influence on cells, although the C1 product demonstrated a more extensive healing mechanism. Histological examination of the kidney and liver tissues revealed no evidence of toxicity. There were no notable negative outcomes in the treated groups, demonstrating the biocompatibility and efficacy of these bioproducts. By day 15, the skin of both groups had healed completely. This research introduces a pioneering strategy by utilizing composite cements, traditionally used in dentistry, in the context of skin wound healing.
Effect of Spectral Filtering and Segmental X-ray Tube Current Switch-Off on Interventionalist’s Scatter Exposure during CT Fluoroscopy
Authors: Grosser Oliver S. , Volk Martin , Georgiades Marilena , Punzet Daniel , Alsawalhi Bahaa , Kupitz Dennis , Omari Jazan , Wissel Heiko , Kreissl Michael C. , Rose Georg , Pech Maciej
Published: August 2024

Dose optimization in computed tomography (CT) is crucial, especially in CT fluoroscopy (fluoro-CT) used for real-time navigation, affecting both patient and operator safety. This study evaluated the impact of spectral X-ray filtering using a tin filter (Sn filter), and a method called partial-angle computed tomography (PACT), which involves segmentally switching off the X-ray tube current at the ambient dose rate H˙*(10) at the interventional radiologist’s (IR) position. Measurements were taken at two body regions (upper body: head/neck; lower body: lower legs/feet) using a 120 kV X-ray tube voltage, 3 × 5.0 mm CT collimation, 0.5 s rotation speed, and X-ray tube currents of 43 Eff.mAs (without Sn filter) and 165 Eff.mAs (with Sn filter). The study found significant dose reductions in both body regions when using the Sn filter and PACT together. For instance, in the upper body region, the combination protocol reduced H˙*(10) from 11.8 µSv/s to 6.1 µSv/s (p < 0.0001) compared to the protocol without using these features. Around 8% of the reduction (about 0.5 µSv/s) is attributed to the Sn filter (p = 0.0005). This approach demonstrates that using the Sn filter along with PACT effectively minimizes radiation exposure for the IR, particularly protecting areas like the head/neck, which can only be insufficiently covered by (standard) radiation protection material.
Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation
Authors: Mizuno Yumi , Tamaru Shunsuke , Tochigi Hideno , Sato Tomomi , Kishi Miyuko , Ohtake Akira , Ishihara Osamu , Kajihara Takeshi
Published: August 2024

Decidualization denotes the morphological and biological differentiating process of human endometrial stromal cells (HESCs). Fatty acid pathways are critical for endometrial decidualization. However, the participation of fatty acids as an energy source and their role in endometrial decidualization have received little attention. To identify fatty acids and clarify their role in decidualization, we comprehensively evaluated free fatty acid profiles using liquid chromatography/Fourier transform mass spectrometry (LC/FT-MS). LC/FT-MS analysis detected 26 kinds of fatty acids in the culture medium of decidualized or un-decidualized HESCs. Only the production of octanoic acid, which is an essential energy source for embryonic development, was increased upon decidualization. The expressions of genes related to octanoic acid metabolism including ACADL, ACADM, and ACADS; genes encoding proteins catalyzing the first step of mitochondrial fatty acid beta-oxidation; and ACSL5 and ACSM5; genes encoding fatty acid synthesis proteins were significantly altered upon decidualization. These results suggest that decidualization promotes lipid metabolism, implying that decidualized HESCs require energy metabolism of the mitochondria in embryo implantation.
Integrating Signaling Pathways with Transcription Factor Networks—On the Trail of Sisyphus?
Authors: Papavassiliou Kostas A. , Papavassiliou Athanasios G.
Published: August 2024

In the context of health and disease research, cells use signaling pathways that transduce stimuli from the extracellular environment to modulate intracellular gene expression via the activity of transcription factors and cofactors (coactivators and/or corepressors) [...]
Creating Meiotic Recombination-Regulating DNA Sites by SpEDIT in Fission Yeast Reveals Inefficiencies, Target-Site Duplications, and Ectopic Insertions
Authors: Protacio Reine U. , Dixon Seth , Davidson Mari K. , Wahls Wayne P.
Published: August 2024

Recombination hotspot-activating DNA sites (e.g., M26, CCAAT, Oligo-C) and their binding proteins (e.g., Atf1-Pcr1 heterodimer; Php2-Php3-Php5 complex, Rst2, Prdm9) regulate the distribution of Spo11 (Rec12)-initiated meiotic recombination. We sought to create 14 different candidate regulatory DNA sites via bp substitutions in the ade6 gene of Schizosaccharomyces pombe. We used a fission yeast-optimized CRISPR-Cas9 system (SpEDIT) and 196 bp-long dsDNA templates with centrally located bp substitutions designed to ablate the genomic PAM site, create specific 15 bp-long DNA sequences, and introduce a stop codon. After co-transformation with a plasmid that encoded both the guide RNA and Cas9 enzyme, about one-third of colonies had a phenotype diagnostic for DNA sequence changes at ade6. PCR diagnostics and DNA sequencing revealed a diverse collection of alterations at the target locus, including: (A) complete or (B) partial template-directed substitutions; (C) non-homologous end joinings; (D) duplications; (E) bp mutations, and (F) insertions of ectopic DNA. We concluded that SpEDIT can be used successfully to generate a diverse collection of DNA sequence elements within a reporter gene of interest. However, its utility is complicated by low efficiency, incomplete template-directed repair events, and undesired alterations to the target locus.
Novel Insights into the Antimicrobial and Antibiofilm Activity of Pyrroloquinoline Quinone (PQQ); In Vitro, In Silico, and Shotgun Proteomic Studies
Authors: Labib Mai M. , Alqahtani Alaa M. , Abo Nahas Hebatallah H. , Aldossari Rana M. , Almiman Bandar Fahad , Ayman Alnumaani Sarah , El-Nablaway Mohammad , Al-Olayan Ebtesam , Alsunbul Maha , Saied Essa M.
Published: August 2024

Microbial infections pose a significant global health threat, affecting millions of individuals and leading to substantial mortality rates. The increasing resistance of microorganisms to conventional treatments requires the development of novel antimicrobial agents. Pyrroloquinoline quinone (PQQ), a natural medicinal drug involved in various cellular processes, holds promise as a potential antimicrobial agent. In the present study, our aim was, for the first time, to explore the antimicrobial activity of PQQ against 29 pathogenic microbes, including 13 fungal strains, 8 Gram-positive bacteria, and 8 Gram-negative bacteria. Our findings revealed potent antifungal properties of PQQ, particularly against Syncephalastrum racemosum, Talaromyces marneffei, Candida lipolytica, and Trichophyton rubrum. The MIC values varied between fungal strains, and T. marneffei exhibited a lower MIC, indicating a greater susceptibility to PQQ. In addition, PQQ exhibited notable antibacterial activity against Gram-positive and -negative bacteria, with a prominent inhibition observed against Staphylococcus epidermidis, Proteus vulgaris, and MRSA strains. Remarkably, PQQ demonstrated considerable biofilm inhibition against the MRSA, S. epidermidis, and P. vulgaris strains. Transmission electron microscopy (TEM) studies revealed that PQQ caused structural damage and disrupted cell metabolism in bacterial cells, leading to aberrant morphology, compromised cell membrane integrity, and leakage of cytoplasmic contents. These findings were further affirmed by shotgun proteomic analysis, which revealed that PQQ targets several important cellular processes in bacteria, including membrane proteins, ATP metabolic processes, DNA repair processes, metal-binding proteins, and stress response. Finally, detailed molecular modeling investigations indicated that PQQ exhibits a substantial binding affinity score for key microbial targets, including the mannoprotein Mp1P, the transcriptional regulator TcaR, and the endonuclease PvuRTs1I. Taken together, our study underscores the effectiveness of PQQ as a broad-spectrum antimicrobial agent capable of combating pathogenic fungi and bacteria, while also inhibiting biofilm formation and targeting several critical biological processes, making it a promising therapeutic option for biofilm-related infections.
Regional Variability in MRI Scans with Different Magnetic Field Strengths in Japan: Implications for Healthcare Preparedness for Alzheimer’s Disease Treatment
Authors: Sato Kenichiro , Niimi Yoshiki , Ihara Ryoko , Iwata Atsushi , Iwatsubo Takeshi
Published: August 2024

(1) Background: The 2023 approval of lecanemab for early-stage Alzheimer’s disease (AD) highlighted the need for routine 1.5T or 3.0T MRI scans to monitor amyloid-related imaging abnormalities (ARIAs). Regional disparities in MRI scan frequency, MRI scanner availability, and scanner magnetic field strengths could affect readiness for anti-amyloid therapy and lead to inconsistencies in ARIA detection nationwide. (2) Methods: We assessed regional variance in MRI scan frequency and field strength across Japan using the National Database (NDB) Open Data website, which summarizes Japanese public health insurance claims from the fiscal years (FYs) 2015 to 2021. We employed a mixed-effects model with prefecture-level random intercepts and slopes over time, subsequently categorizing prefectures into clusters based on MRI usage. (3) Results: 1.5T MRI was the most common magnetic field strength, remaining stable from FY2015 to FY2021. 3.0T MRI usage slightly increased, although the COVID-19 pandemic in FY2020 led to a maximum reduction of 5%. Prefecture-level variance was higher for 3.0T MRIs, with more frequent usage in western Japan. (4) Conclusions: This study highlights prefecture-level variance in MRI usage across Japan. The insights gained could be instrumental in improving healthcare preparedness for anti-amyloid treatment and patient management.
The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review
Authors: Zikou Eva , Koliaki Chrysi , Makrilakis Konstantinos
Published: August 2024

The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.
Characterization of a Novel Oxidative Stress Responsive Transcription Regulator in Mycobacterium bovis
Authors: Jiang Qiang , Hu Rong , Liu Feng , Huang Feng , Zhang Lei , Zhang Hua
Published: August 2024

The antioxidant defense is critical for the survival of intracellular pathogens such as Mycobacterium tuberculosis complex (MTBC) species, including Mycobacterium bovis, which are often exposed to an oxidative environment caused by reactive oxygen species (ROS) in hosts. However, the signaling pathway in mycobacteria for sensing and responding to oxidative stress remains largely unclear. In this study, we characterize a TetR-type transcription regulator BCG_3893c, designated AotM, as a novel redox sensor in Mycobacterium bovis that increases mycobacterial tolerance to oxidative stress. AotM is required for the growth of M. bovis in the presence of 1 mM hydrogen peroxide. Loss of the aotM gene leads to altered transcriptional profiles with 352 genes significantly up-regulated and 25 genes significantly down-regulated. AotM recognizes a 14-bp palindrome sequence motif and negatively regulates the expression of a FAD-dependent oxidoreductase encoded by bcg_3892c. Overexpression of BCG_3892c increases intracellular ROS production and reduces the growth of M. bovis. In summary, we propose that AotM enhances the mycobacterial resistance against oxidative stress probably by inhibiting intracellular ROS production. Our findings reveal a novel underlying regulatory mechanism behind mycobacterial oxidative stress adaptation.
Dysregulated Non-Coding RNA Expression in T Cells from Patients with Ankylosing Spondylitis Contributes to Its Immunopathogenesis
Authors: Yu Hui-Chun , Wang Sz-Tsan , Lu Ming-Chi
Published: August 2024

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by inflammatory back pain and bony fusion of vertebral joints. Genetic associations and environmental factors have been proposed to explain the immunopathogenesis of AS. In the past few years, there have been major advances in understanding T cell dysfunction in AS. Clinically, targeting interleukin-17A, a major cytokine secreted by T helper 17 cells, has been approved for treating patients with active AS. Non-coding RNAs (ncRNAs) are RNA transcripts that do not translate into proteins. The ncRNAs regulate both innate and adaptive immunity and participate in the pathogenesis of autoimmune diseases, including AS. The main purpose of this article is to review the up-to-date studies investigating the aberrant expression of ncRNAs in T cells from patients with AS and to summarize their roles in its pathogenesis. After searching PubMed for studies published between January 2013 and June 2024, nine studies investigating the expression of ncRNAs in AS T cells were included. We found that aberrantly expressed ncRNAs in AS T cells could cause abnormal cytokine release, cell signaling abnormalities, and dysregulated cell proliferation and death, which contribute to the immunopathogenesis of AS. We discussed some limitations of these studies and suggested several research fields for further investigation.
Diagnostic and Therapeutic Approaches for Heart Failure in Long-Term Survivors of Childhood Cancer
Authors: Fernandez-Aviles Consuelo , Gonzalez-Manzanares Rafael , Ojeda Soledad , Castillo Juan C. , Robles-Mezcua Ainhoa , Anguita Manuel , Mesa Dolores , Pan Manuel
Published: August 2024

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies. This review aims to summarize the latest findings in the diagnosis and treatment of cancer therapy-related cardiac disease in long-term survivors of childhood cancer, with a focus on heart failure.
Application of PPAR Ligands and Nanoparticle Technology in Metabolic Steatohepatitis Treatment
Authors: Vu Hung Thai , Nguyen Vien Duc , Ikenaga Hiroko , Matsubara Tsutomu
Published: August 2024

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is a major disease worldwide whose effective treatment is challenging. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and function as ligand-activated transcription factors. To date, three distinct subtypes of PPARs have been characterized: PPARα, PPARβ/δ, and PPARγ. PPARα and PPARγ are crucial regulators of lipid metabolism that modulate the transcription of genes involved in fatty acid (FA), bile acid, and cholesterol metabolism. Many PPAR agonists, including natural (FAs, eicosanoids, and phospholipids) and synthetic (fibrate, thiazolidinedione, glitazar, and elafibranor) agonists, have been developed. Furthermore, recent advancements in nanoparticles (NPs) have led to the development of new strategies for MASLD/MASH therapy. This review discusses the applications of specific cell-targeted NPs and highlights the potential of PPARα- and PPARγ-targeted NP drug delivery systems for MASLD/MASH treatment.
Heart Rate Variability and Functional Outcomes of Patients with Spontaneous Intracerebral Hemorrhage
Authors: Laichinger Kornelia , Mengel Annerose , Buesink Rebecca , Roesch Sara , Stefanou Maria-Ioanna , Single Constanze , Hauser Till-Karsten , Krumbholz Markus , Ziemann Ulf , Feil Katharina
Published: August 2024

Background: The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients. Methods: We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0–2, 0–8, 0–12, 0–24, 0–48, 0–72, and 8–16, 16–24, 24–48, 48–72, 72–96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0–2. Results: The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0–72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0–72 h: OR 0.898; CI 0.800–1.008; p = 0.067). Conclusions: Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days.
Deep Learning for MRI Segmentation and Molecular Subtyping in Glioblastoma: Critical Aspects from an Emerging Field
Authors: Bonada Marta , Rossi Luca Francesco , Carone Giovanni , Panico Flavio , Cofano Fabio , Fiaschi Pietro , Garbossa Diego , Di Meco Francesco , Bianconi Andrea
Published: August 2024

Deep learning (DL) has been applied to glioblastoma (GBM) magnetic resonance imaging (MRI) assessment for tumor segmentation and inference of molecular, diagnostic, and prognostic information. We comprehensively overviewed the currently available DL applications, critically examining the limitations that hinder their broader adoption in clinical practice and molecular research. Technical limitations to the routine application of DL include the qualitative heterogeneity of MRI, related to different machinery and protocols, and the absence of informative sequences, possibly compensated by artificial image synthesis. Moreover, taking advantage from the available benchmarks of MRI, algorithms should be trained on large amounts of data. Additionally, the segmentation of postoperative imaging should be further addressed to limit the inaccuracies previously observed for this task. Indeed, molecular information has been promisingly integrated in the most recent DL tools, providing useful prognostic and therapeutic information. Finally, ethical concerns should be carefully addressed and standardized to allow for data protection. DL has provided reliable results for GBM assessment concerning MRI analysis and segmentation, but the routine clinical application is still limited. The current limitations could be prospectively addressed, giving particular attention to data collection, introducing new technical advancements, and carefully regulating ethical issues.
Editorial of the Special Issue “Molecular Research and Recent Advances in Diabetic Retinopathy”
Authors: Bulum Tomislav , Tomić Martina
Published: August 2024

Despite increasing awareness of diabetes and its devastating complications, it remains the most rapidly escalating global health issue [...]
Multiwavelength Photoacoustic Doppler Flowmetry of Living Microalgae Cells
Authors: Farooq Tayyab , Wu Xiuru , Yan Sheng , Fang Hui
Published: August 2024

Photoacoustics can provide a direct measurement of light absorption by microalgae depending on the photosynthesis pigment within them. In this study, we have performed photoacoustic flowmetry on living microalgae cells to measure their flow characteristics, which include flow speed, flow angle, flow direction, and, more importantly, the photoacoustic absorption spectrum, all by observing the photoacoustic Doppler power spectra during their flowing state. A supercontinuum pulsed laser with a high repetition frequency is used as the light source: through intensity modulation at a specified frequency, it can provide wavelength-selectable excitation of a photoacoustic signal centered around this frequency. Our approach can be useful to simultaneously measure the flow characteristics of microalgae and easily discriminate their different species with high accuracy in both static and dynamic states, thus facilitating the study of their cultivation and their role in our ecosystem.
The Relationship between Clinical and Psychophysical Assessments of Visual Perceptual Disturbances in Individuals at Clinical High Risk for Psychosis: A Preliminary Study
Authors: Ifrah Chloe , Herrera Shaynna N. , Silverstein Steven M. , Corcoran Cheryl M. , Gordon James , Butler Pamela D. , Zemon Vance
Published: August 2024

This study investigated relations between a measure of early-stage visual function and self-reported visual anomalies in individuals at clinical high risk for psychosis (CHR-P). Eleven individuals at CHR identified via the Structured Interview for Psychosis-Risk Syndromes (SIPS) were recruited from a CHR-P research program in NYC. The sample was ~36% female, ranging from 16 to 33 years old (M = 23.90, SD = 6.14). Participants completed a contrast sensitivity task on an iPad with five spatial frequencies (0.41–13 cycles/degree) and completed the self-report Audio-Visual Abnormalities Questionnaire. Higher contrast sensitivity (better performance) to low spatial frequencies was associated with higher perceptual (r = 0.616, p = 0.044) and visual disturbances (r = 0.667, p = 0.025); lower contrast sensitivity to a middle spatial frequency was also associated with higher perceptual (r = −0.604, p = 0.049) and visual disturbances (r = −0.606, p = 0.048). This relation between the questionnaire and contrast sensitivity to low spatial frequency may be indicative of a reduction in lateral inhibition and “flooding” of environmental stimuli. The association with middle spatial frequencies, which play a critical role in face processing, may result in a range of perceptual abnormalities. These findings demonstrate that self-reported perceptual anomalies occur in these individuals and are linked to performance on a measure of early visual processing.
Neurological Damage Measured by S-100b and Neuron-Specific Enolase in Patients Treated with Electroconvulsive Therapy
Authors: Ruiz-Chow Ángel A. , López-Cruz Carlos J. , Crail-Meléndez Daniel , Ramírez-Bermúdez Jesús , Santos-Zambrano José , Luz-Escamilla Laura A.
Published: August 2024

Electroconvulsive therapy (ECT) is considered one of the most effective treatments for psychiatric disorders. ECT has proven effective in the treatment of depression, mania, catatonia and psychosis. It is presumed that seizures induced during ECT administration cause toxicity and potentially neuronal and glial cell death. A broad range of neurological disorders increase cerebrospinal fluid and serum levels of neuron-specific enolase (NSE) and S-100b protein. This study aims to investigate the effect of ECT on NSE and S-100b levels, which, together, serve as a proxy for neuronal cell damage. Serum concentrations of S-100b and NSE of adult patients who received ECT were measured by immunoluminometric analysis before and after treatment. A two-way ANOVA test was used to estimate the statistical differences in marker concentrations between the subgroups of the study population. Results: A total of 55 patients were included in the analysis: 52.73% (n = 29) were diagnosed with depression, 21.82% (n = 12) with schizophrenia or other psychosis, 16.36% (n = 9) with mania and 9.09% (n = 5) with catatonia. There were no statistically significant changes in NSE (p = 0.288) and S-100b (p = 0.243) levels. We found no evidence that ECT induced neuronal damage based on NSE and S-100b protein levels measured in the serum of patients before and after treatment.