bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Raman Spectral Based Classifications with Convolutional Neural Networks Using Practical Examples of Fungal Spores and Carotenoid-Pigmented Microorganisms
Authors: Tewes Thomas J. , Welle Michael C. , Hetjens Bernd T. , Tipatet Kevin Saruni , Pavlov Svyatoslav , Platte Frank , Bockmühl Dirk P.
Published: January 2023

Numerous publications showing that robust prediction models for microorganisms based on Raman micro-spectroscopy in combination with chemometric methods are feasible, often with very precise predictions. Advances in machine learning and easier accessibility to software make it increasingly easy for users to generate predictive models from complex data. However, the question regarding why those predictions are so accurate receives much less attention. In our work, we use Raman spectroscopic data of fungal spores and carotenoid-containing microorganisms to show that it is often not the position of the peaks or the subtle differences in the band ratios of the spectra, due to small differences in the chemical composition of the organisms, that allow accurate classification. Rather, it can be characteristic effects on the baselines of Raman spectra in biochemically similar microorganisms that can be enhanced by certain data pretreatment methods or even neutral-looking spectral regions can be of great importance for a convolutional neural network. Using a method called Gradient-weighted Class Activation Mapping, we attempt to peer into the black box of convolutional neural networks in microbiological applications and show which Raman spectral regions are responsible for accurate classification.
A Brief Survey of Methods for Analytics over RDF Knowledge Graphs
Authors: Papadaki Maria-Evangelia , Tzitzikas Yannis , Mountantonakis Michalis
Published: January 2023

There are several Knowledge Graphs expressed in RDF (Resource Description Framework) that aggregate/integrate data from various sources for providing unified access services and enabling insightful analytics. We observe this trend in almost every domain of our life. However, the provision of effective, efficient, and user-friendly analytic services and systems is quite challenging. In this paper we survey the approaches, systems and tools that enable the formulation of analytic queries over KGs expressed in RDF. We identify the main challenges, we distinguish two main categories of analytic queries (domain specific and quality-related), and five kinds of approaches for analytics over RDF. Then, we describe in brief the works of each category and related aspects, like efficiency and visualization. We hope this collection to be useful for researchers and engineers for advancing the capabilities and user-friendliness of methods for analytics over knowledge graphs.
Acknowledgment to the Reviewers of Analytics in 2022
Authors:   Analytics Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Helicobacter pylori Infection: Current Status and Future Prospects on Diagnostic, Therapeutic and Control Challenges
Authors: Elbehiry Ayman , Marzouk Eman , Aldubaib Musaad , Abalkhail Adil , Anagreyyah Sulaiman , Anajirih Nuha , Almuzaini Abdulaziz M. , Rawway Mohammed , Alfadhel Abdulmajeed , Draz Abdelmaged , Abu-Okail Akram
Published: January 2023

Helicobacter pylori (H. pylori) infection, which affects approximately half of the world’s population, remains a serious public health problem. As H. pylori infection leads to a number of gastric pathologies, including inflammation, gastroduodenal ulcers, and malignancies, early detection and treatment are crucial to preventing the spread of the infection. Multiple extragastric complications, such as iron deficiency anaemia, immune thrombocytopenic purpura, vitamin B12 deficiency, diabetes mellitus, cardiovascular diseases, and certain neurological disorders, have also been linked to H. pylori infection. An awareness of H. pylori and associated health hazards is necessary to minimize or even eradicate the infection. Therefore, there is an urgent need to raise the standards for the currently employed diagnostic, eradication, alternative treatment strategies. In addition, a brief overview of traditional and cutting-edge approaches that have proven effective in identifying and managing H. pylori is needed. Based on the test and laboratory equipment available and patient clinical characteristics, the optimal diagnostic approach requires weighing several factors. The pathophysiology and pathogenic mechanisms of H. pylori should also be studied, focusing more on the infection-causing virulence factors of this bacterium. Accordingly, this review aims to demonstrate the various diagnostic, pathophysiological, therapeutic, and eradication tactics available for H. pylori, emphasizing both their advantages and disadvantages. Invasive methods (such as quick urease testing, biopsy, or culture) or noninvasive methods (such as breath tests, stool investigations, or serological tests) can be used. We also present the most recent worldwide recommendations along with scientific evidence for treating H. pylori. In addition to the current antibiotic regimens, alternative therapies may also be considered. It is imperative to eradicate the infections caused by H. pylori as soon as possible to prevent problems and the development of stomach cancer. In conclusion, significant advances have been made in identifying and treating H. pylori. To improve eradication rates, peptide mass fingerprinting can be used as a diagnostic tool, and vaccines can also eliminate the infection.
Evaluation of an Antifungal Stewardship Initiative Targeting Micafungin at an Academic Medical Center
Authors: Keck J. Myles , Cretella David A. , Stover Kayla R. , Wagner Jamie L. , Barber Katie E. , Jhaveri Tulip A. , Vijayvargiya Prakhar , Garrigos Zerelda Esquer , Wingler Mary Joyce B.
Published: January 2023

Delays in the treatment of proven invasive fungal disease have been shown to be harmful. However, empiric treatment for all patients at risk of infection has not demonstrated benefit. This study evaluates the effects of a micafungin stewardship initiative on the duration of therapy and clinical outcomes at the University of Mississippi Medical Center in Jackson, Mississippi. This single-center quasi-experiment evaluated patients who received micafungin. Adult inpatients who received at least one treatment dose of micafungin in the pre-intervention (1 October 2020 to 30 September 2021) or post-intervention (1 October 2021 to 30 April 2022) groups were included. Patients were placed on micafungin for prophylaxis and those who required definitive micafungin therapy were excluded. An algorithm was used to provide real-time recommendations in order to assess change in the treatment days of micafungin therapy. A total of 282 patients were included (141 pre-group versus 141 post-group). Over 80% of the patients included in the study were in an intensive care unit, and other baseline characteristics were similar. The median number of treatment days with micafungin was 4 [IQR 3-6] in the pre-group and 3 [IQR 2-6] in the post-group (p = 0.005). Other endpoints, such as time to discontinuation or de-escalation, hospital mortality, and hospital length of stay, were not significantly different between the groups. An antifungal stewardship initiative can be an effective way to decrease unnecessary empiric antifungal therapy for patients who are at risk of invasive fugal disease.
Uncovering the Secretion Systems of Acinetobacter baumannii: Structures and Functions in Pathogenicity and Antibiotic Resistance
Authors: Li Pu , Zhang Sirui , Wang Jingdan , Al-Shamiri Mona Mohamed , Han Bei , Chen Yanjiong , Han Shaoshan , Han Lei
Published: January 2023

Infections led by Acinetobacter baumannii strains are of great concern in healthcare environments due to the strong ability of the bacteria to spread through different apparatuses and develop drug resistance. Severe diseases can be caused by A. baumannii in critically ill patients, but its biological process and mechanism are not well understood. Secretion systems have recently been demonstrated to be involved in the pathogenic process, and five types of secretion systems out of the currently known six from Gram-negative bacteria have been found in A. baumannii. They can promote the fitness and pathogenesis of the bacteria by releasing a variety of effectors. Additionally, antibiotic resistance is found to be related to some types of secretion systems. In this review, we describe the genetic and structural compositions of the five secretion systems that exist in Acinetobacter. In addition, the function and molecular mechanism of each secretion system are summarized to explain how they enable these critical pathogens to overcome eukaryotic hosts and prokaryotic competitors to cause diseases.
A Validated UHPLC–MS/MS Method to Quantify Eight Antibiotics in Quantitative Dried Blood Spots in Support of Pharmacokinetic Studies in Neonates
Authors: Liu Qian , Liu Lanyu , Yuan Yu , Xie Feifan
Published: January 2023

Objectives: Conduction of pharmacokinetic (PK) study in pediatric patients is challenging due to blood sampling limits. The dried blood spots (DBS) method represents a potential matrix for microsampling in support of PK studies in children. Herein, we used the Capitainer® qDBS device to develop a DBS method that can collect an exact 10 µL volume of blood on a paper card. This DBS method was developed to simultaneously quantify the concentrations of eight antibiotics, including sulbactam, tazobactam, ampicillin, meropenem, cefotaxime, cefoperazone, piperacillin, and metronidazole using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Methods: The prepared DBS samples were extracted in methanol containing acetaminophen as the internal standard at 20 °C on a block bath shaker at 500 rpm for 30 min. The extracted antibiotics were eluted on an Acquity UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) using gradient elution with a total chromatographic run time of 6.5 min. The precursor and product ions of the analytes were detected by use of the multiple reaction monitoring (MRM) mode. Results: No interfering peaks at the respective retention times of the analytes were observed in DBS samples. The lower limits of quantification (LLOQ) for the antibiotics were between 0.25 and 2.0 μg/mL, and satisfactory accuracies (intra/inter-assay bias −16.7 to +13.6%) and precisions (intra/inter-assay coefficient of variations 1.5–15.6%) were obtained for the analytes. As a proof of concept, the method was applied to DBS samples obtained from neonatal patients treated with ampicillin and piperacillin/sulbactam. Conclusions: The DBS method is simple and robust, and it can be used in children with limited blood sampling.
Aging-Associated Thyroid Dysfunction Contributes to Oxidative Stress and Worsened Functional Outcomes Following Traumatic Brain Injury
Authors: Hsieh Cheng-Ta , Yen Ting-Lin , Chen Yu-Hao , Jan Jing-Shiun , Teng Ruei-Dun , Yang Chih-Hao , Sun Jui-Ming
Published: January 2023

The incidence of traumatic brain injury (TBI) increases dramatically with advanced age and accumulating evidence indicates that age is one of the important predictors of an unfavorable prognosis after brain trauma. Unfortunately, thus far, evidence-based effective therapeutics for geriatric TBI is limited. By using middle-aged animals, we first confirm that there is an age-related change in TBI susceptibility manifested by increased inflammatory events, neuronal death and impaired functional outcomes in motor and cognitive behaviors. Since thyroid hormones function as endogenous regulators of oxidative stress, we postulate that age-related thyroid dysfunction could be a crucial pathology in the increased TBI severity. By surgically removing the thyroid glands, which recapitulates the age-related increase in TBI-susceptible phenotypes, we provide direct evidence showing that endogenous thyroid hormone-dependent compensatory regulation of antioxidant events modulates individual TBI susceptibility, which is abolished in aged or thyroidectomized individuals. The antioxidant capacity of melatonin is well-known, and we found acute melatonin treatment but not liothyronine (T3) supplementation improved the TBI-susceptible phenotypes of oxidative stress, excitotoxic neuronal loss and promotes functional recovery in the aged individuals with thyroid dysfunction. Our study suggests that monitoring thyroid function and acute administration of melatonin could be feasible therapeutics in the management of geriatric-TBI in clinic.
Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms
Authors: Torrisi Filippo , D’Aprile Simona , Denaro Simona , Pavone Anna Maria , Alberghina Cristiana , Zappalà Agata , Giuffrida Rosario , Salvatorelli Lucia , Broggi Giuseppe , Magro Gaetano Giuseppe , Calabrese Vittorio , Vicario Nunzio , Parenti Rosalba
Published: January 2023

The central nervous system represents a complex environment in which glioblastoma adapts skillfully, unleashing a series of mechanisms suitable for its efficient development and diffusion. In particular, changes in gene expression and mutational events that fall within the domain of epigenetics interact complexly with metabolic reprogramming and stress responses enacted in the tumor microenvironment, which in turn fuel genomic instability by providing substrates for DNA modifications. The aim of this review is to analyze this complex interaction that consolidates several conditions that confer a state of immunosuppression and immunoevasion, making glioblastoma capable of escaping attack and elimination by immune cells and therefore invincible against current therapies. The progressive knowledge of the cellular mechanisms that underlie the resistance of the glioblastoma represents, in fact, the only weapon to unmask its weak points to be exploited to plan successful therapeutic strategies.
An Approach to the Semantic Representation of the Local Government Strategic Planning Process: Ontology-Driven Simulation Method for Assessing Economic Impacts
Authors: Zarić Miroslav , Arsovski Saša , Markoski Branko , Vasiljević Petar , Premčevski Velibor
Published: January 2023

This paper describes a methodological approach to the creation of a strategic planning ontology (SPO) for local governments. The aim of the given ontology is to provide a semantic description of the development strategy, involved stakeholders, and tools to improve the decision-making process for selecting the most valuable strategic objectives for the economy of the region. The novelty of the research presented in this paper is reflected by the development of an ontological model of actions and reasons, that is, semantically described combinations of activities and requirements that are defined by development strategies. The proposed ontology can provide answers to questions such as: what are the development priorities? How will those priorities be implemented? Who will be responsible for implementation? Why are they being implemented in the first place? We answer the question, “why specific development goals are chosen?”. Answers are given as semantic representations of the economic impact on a region’s industry. The ontology-driven simulation methods that are proposed in this paper provide the possibility of simulating the effects and results of the chosen development strategy goals, evaluate the actions taken, and ensure support for the selection of the best alternative in the process of defining objectives for the development strategy.
The Strain Distribution Reconstructions Using GWO Algorithm and Verification by FBG Experimental Data
Authors: Zhang Meng , Wang Jingyan , Xiong Xiao , Chen Zihan , Gong Ying , Gao Sisi , Zhang Weifang
Published: January 2023

A structural strain reconstruction based on the grey wolf optimizer (GWO) algorithm using fiber Bragg grating (FBG) sensors is described in this paper. The fiber strain data obtained by the GWO algorithm and a modified transfer-matrix method (TMM) are verified by experimental data obtained using the digital image correlation (DIC) method. In the GWO algorithm, the optimization goal is set as the minimum error between the target experimental deformation spectrum and a random simulation strain spectrum, and the strain reconstruction is obtained by means of continuous iterative optimization. The validity of this method is confirmed by experimental strain data obtained by DIC, and the verification results show that the method proposed in this paper can be used as an accurate and efficient method of strain reconstruction.
Assessment and Categorization of Biological Effects and Atypical Symptoms Owing to Exposure to RF Fields from Wireless Energy Devices
Authors: Razek Adel
Published: January 2023

Nowadays, environmental electromagnetic fields exist everywhere and the whole population is exposed. The most widespread technologies engendering exposure to electromagnetic fields for the public and workers are radiofrequency wireless communication systems. Such exposure can have direct effects on living tissue involving biological problems or personal symptoms, as well as indirect effects restricting healthcare appliances. This assessment aims to analyze, examine and categorize the consequences of non-ionizing electromagnetic fields emitted by radiofrequency devices. This concerns biological effects in living tissues and atypical personal symptoms for short and long-term exposures. The evaluation methodology in this field of investigation is also discussed. In the article, these consequences as well as their evaluation techniques, in the case of wireless digital communication tools, are analyzed and reviewed. The categorization of exposure sources, the corresponding effects and their assessment methodologies are analyzed. The concept of systematic reviews and meta-analyses and their applications in various assessments of these effects and symptoms are reviewed and discussed.
A Comparative Study in Forming Behavior of Different Grades of Steel in Cold Forging Backward Extrusion by Integrating Artificial Neural Network (ANN) with Differential Evolution (DE) Algorithm
Authors: Petkar Praveenkumar M. , Gaitonde Vinayak N. , Kulkarni Vinayak N. , Karnik Ramesh S. , Davim João Paulo
Published: January 2023

The cold forging backward extrusion is employed to produce parts that are characterized by better mechanical strength. However, in this process, punches are often prone to breakages because of the large forces encountered in deforming the steel billets. The service life of the punches is affected majorly by the geometrical attributes, the type of steel undergoing deformation, and hence the present investigation focuses on the applications of natural computing algorithms such as artificial neural network (ANN) and differential evolution (DE) optimization algorithm to study the differential influence on the forming behavior of different grades steel and enhance the punch service life. The AISI steel grades, such as AISI 1010, 1018, and 1045, employed extensively in the production of automotive components, have been compared in terms of forming behavior, such as effective stress, strain, strain rate, and punch force. The multi-layer feed-forward ANN architecture was utilized for process modeling with forming responses of finite element (FE) simulations that are strategically planned through the design of experiments (DoE) approach. Considerable variations were found for the effective stress and punch force amongst the steels, while marginal deviations were observed for effective strain and strain rates. Confirmatory experiments were conducted to validate the results of optimal combinations obtained through the DE optimization technique, and the deviations were observed to be in the acceptable range. The cold forging backward extruded components have also been examined for better mechanical soundness through microstructure and micro-hardness analysis that clearly revealed the mechanical integrity and strength enhancement within the forged components. The proposed study would assist the industries engaged in the production of cold-forged steel components in determining the appropriate values of variables to minimize the forming responses and, thus, help in enhancing the life of the tooling.
Acknowledgment to the Reviewers of Advances in Respiratory Medicine in 2022
Authors:   Advances in Respiratory Medicine Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Differential Analysis of the Positron Impact Ionization of Hydrogen in Debye Plasmas
Authors: Acebal Emiliano , Martínez Sergio Hernan , Otranto Sebastian
Published: January 2023

In this work, a theoretical differential analysis of the positron impact ionization of hydrogen embedded in weakly coupled plasmas at an impact energy of 80 eV is developed. While the total and singly differential cross sections are analyzed within the classical trajectory Monte Carlo method, a Born-3DW model for screened environments, recently introduced by the authors, is used to provide a fully differential view of the process. The present results suggest that the electron emission spectra are strongly affected by the level of screening of the surrounding medium, mainly due to the loss of the postcollisional interaction mechanism.
Changes in the Mechanical Behavior of Electrically Aged Lithium-Ion Pouch Cells: In-Plane and Out-of-Plane Indentation Loads with Varying Testing Velocity and State of Charge
Authors: Sprenger Marvin , Kovachev Georgi , Dölle Norbert , Schauwecker Florian , Sinz Wolfgang , Ellersdorfer Christian
Published: January 2023

The knowledge about the influence of electrical aging on the behavior of lithium-ion cells under mechanical loads is of high importance to ensure a safe use of batteries over the lifetime in electric vehicles. In order to describe the mechanical behavior in relation to electrical aging, fresh and electrically aged NCM pouch cells were investigated under different mechanical crash loads. For the first time, the aged cells’ behavior under quasistatic lateral loading was taken into account. Aged cells showed lower maximum forces compared to the fresh cells. The reason of the changed mechanical cell behavior was explained with the different buckling behavior of fresh and aged cells by experimental images. Furthermore, quasistatic and dynamic crash tests in cell’s thickness direction were performed at varying state of charge (SOC) and compared to the results of a previously published study. Independently of the testing velocity, the electrically aged cells failed at increased deformation values. This observation was justified by an increased cell thickness due to an additional softer layer, formed on the aged graphite particle surface, which was observed by the means of scanning electron microscopy. Furthermore, the aged cells showed lower failure forces of up to −11% under quasistatic and dynamic loads at 0% SOC. It was also illustrated that electrical aging causes a deeper voltage drop after cell failure, which suggests a higher energy release after the internal short circuit. The investigations show that electrical aging has a significant influence on the mechanical properties of lithium-ion cells and must be taken into account in the safety assessment.
A Study on the Effect of Particle Size on Li-Ion Battery Recycling via Flotation and Perspectives on Selective Flocculation
Authors: Rinne Tommi , Araya-Gómez Natalia , Serna-Guerrero Rodrigo
Published: January 2023

The recycling of active materials from Li-ion batteries (LIBs) via froth flotation has gained interest recently. To date, recycled graphite has not been pure enough for direct reuse in LIB manufacturing. The present work studied the effect of particle sizes on the grade of recycled graphite. Furthermore, selective flocculation is proposed as a novel approach to control particle sizes and thus improve graphite grade by preventing the entrainment of cathode components. Zeta potential and particle size measurements were performed to find an optimal pH for electrically selective flocculation and to study the interaction of flocculants, respectively. Batch flotation experiments were performed to investigate the effect of particle size on the purity of the recovered graphite. Results suggested that, in the absence of ultrafine fine particles, battery-grade graphite of 99.4% purity could be recovered. In the presence of ultrafine particles, a grade of 98.2% was observed. Flocculating the ultrafine feed increased the grade to 98.4%, although a drop in recovery was observed. By applying a dispersant in addition to a flocculant, the recovery could be increased while maintaining a 98.4% grade. Branched flocculants provided improved selectivity over linear flocculants. The results suggest that particle size needs to be controlled for battery-grade graphite to be recovered.
SARN: Shifted Attention Regression Network for 3D Hand Pose Estimation
Authors: Zhu Chenfei , Hu Boce , Chen Jiawei , Ai Xupeng , Agrawal Sunil K.
Published: January 2023

Hand pose estimation (HPE) plays an important role during the functional assessment of the hand and in potential rehabilitation. It is a challenge to predict the pose of the hand conveniently and accurately during functional tasks, and this limits the application of HPE. In this paper, we propose a novel architecture of a shifted attention regression network (SARN) to perform HPE. Given a depth image, SARN first predicts the spatial relationships between points in the depth image and a group of hand keypoints that determine the pose of the hand. Then, SARN uses these spatial relationships to infer the 3D position of each hand keypoint. To verify the effectiveness of the proposed method, we conducted experiments on three open-source datasets of 3D hand poses: NYU, ICVL, and MSRA. The proposed method achieved state-of-the-art performance with 7.32 mm, 5.91 mm, and 7.17 mm of mean error at the hand keypoints, i.e., mean Euclidean distance between the predicted and ground-truth hand keypoint positions. Additionally, to test the feasibility of SARN in hand movement recognition, a hand movement dataset of 26K depth images from 17 healthy subjects was constructed based on the finger tapping test, an important component of neurological exams administered to Parkinson’s patients. Each image was annotated with the tips of the index finger and the thumb. For this dataset, the proposed method achieved a mean error of 2.99 mm at the hand keypoints and comparable performance on three task-specific metrics: the distance, velocity, and acceleration of the relative movement of the two fingertips. Results on the open-source datasets demonstrated the effectiveness of the proposed method, and results on our finger tapping dataset validated its potential for applications in functional task characterization.
Automated Student Classroom Behaviors’ Perception and Identification Using Motion Sensors
Authors: Wang Hongmin , Gao Chi , Fu Hong , Ma Christina Zong-Hao , Wang Quan , He Ziyu , Li Maojun
Published: January 2023

With the rapid development of artificial intelligence technology, the exploration and application in the field of intelligent education has become a research hotspot of increasing concern. In the actual classroom scenarios, students’ classroom behavior is an important factor that directly affects their learning performance. Specifically, students with poor self-management abilities, particularly specific developmental disorders, may face educational and academic difficulties owing to physical or psychological factors. Therefore, the intelligent perception and identification of school-aged children’s classroom behaviors are extremely valuable and significant. The traditional method for identifying students’ classroom behavior relies on statistical surveys conducted by teachers, which incurs problems such as being time-consuming, labor-intensive, privacy-violating, and an inaccurate manual intervention. To address the above-mentioned issues, we constructed a motion sensor-based intelligent system to realize the perception and identification of classroom behavior in the current study. For the acquired sensor signal, we proposed a Voting-Based Dynamic Time Warping algorithm (VB-DTW) in which a voting mechanism is used to compare the similarities between adjacent clips and extract valid action segments. Subsequent experiments have verified that effective signal segments can help improve the accuracy of behavior identification. Furthermore, upon combining with the classroom motion data acquisition system, through the powerful feature extraction ability of the deep learning algorithms, the effectiveness and feasibility are verified from the perspectives of the dimensional signal characteristics and time series separately so as to realize the accurate, non-invasive and intelligent children’s behavior detection. To verify the feasibility of the proposed method, a self-constructed dataset (SCB-13) was collected. Thirteen participants were invited to perform 14 common class behaviors, wearing motion sensors whose data were recorded by a program. In SCB-13, the proposed method achieved 100% identification accuracy. Based on the proposed algorithms, it is possible to provide immediate feedback on students’ classroom performance and help them improve their learning performance while providing an essential reference basis and data support for constructing an intelligent digital education platform.
Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma
Authors: Suzuki Tomoo , Dai Yidan , Ono Masanori , Kojima Junya , Sasaki Toru , Fujiwara Hiroshi , Kuji Naoaki , Nishi Hirotaka
Published: January 2023

Uterine leiomyomas are smooth-muscle tumors originating in the myometrium and are the most common pelvic tumors in women of reproductive age. Symptomatic tumors may result in abnormal uterine bleeding, bladder dysfunction, pelvic discomfort, and reproductive issues, such as infertility and miscarriage. There are currently few non-invasive treatments for leiomyoma, but there are no practical early intervention or preventive methods. In this study, human uterine leiomyoma and myometrial tissues were used to detect the protein and mRNA expression levels of UCHL1. To explore the effects of UCHL1 knockdown and inhibition in leiomyoma and myometrial cells, we determined the mRNA expressions of COL1A1 and COL3A1. Collagen gel contraction and wound-healing assays were performed on myometrial and leiomyoma cells. We found that UCHL1 expression was considerably higher in uterine leiomyomas than in the myometrium. COL1A1 and COL3A1 expression levels were downregulated after inhibition of UCHL1 in human leiomyoma cells. Furthermore, the elimination of UCHL1 significantly decreased the migration and contractility of leiomyoma cells. In conclusion, these results indicate that UCHL1 is involved in the growth of leiomyoma in humans. For the treatment of uterine leiomyoma, targeting UCHL1 activity may be a unique and possible therapeutic strategy.
Association of Epicardial Adipose Tissue Adipocytes Hypertrophy with Biomarkers of Low-Grade Inflammation and Extracellular Matrix Remodeling in Patients with Coronary Artery Disease
Authors: Kologrivova Irina V. , Naryzhnaya Natalia V. , Koshelskaya Olga A. , Suslova Tatiana E. , Kravchenko Elena S. , Kharitonova Olga A. , Evtushenko Vladimir V. , Boshchenko Alla A.
Published: January 2023

The aim of the study was to compare the morphological features of epicardial adipose tissue (EAT) adipocyte with the circulating inflammatory biomarkers and parameters of extracellular matrix remodeling in patients with coronary artery disease (CAD). We recruited 42 patients with CAD (m/f 28/14) who were scheduled for coronary artery bypass graft surgery (CABG). EAT adipocytes were obtained by the enzymatic method from intraoperative adipose tissue samples. Concentrations of secreted and lipoprotein-associated phospholipase A2 (sPLA2 and LpPLA2), TNF-α, IL-1β, IL-6, IL-10, high-sensitive C-reactive protein (hsCRP), metalloproteinase-9 (MMP-9), MMP-2, C-terminal cross-linking telopeptide of type I collagen (CTX-I), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in blood serum. Patients were divided into two groups: group 1—with mean EAT adipocytes’ size ≤ 87.32 μm; group 2—with mean EAT adipocytes’ size > 87.32 μm. Patients of group 2 had higher concentrations of triglycerides, hsCRP, TNF-α, and sPLA2 and a lower concentration of CTX-I. A multiple logistic regression model was created (RN2 = 0.43, p = 0.0013). Concentrations of TNF-α, sPLA2 and CTX-I appeared to be independent determinants of the EAT adipocyte hypertrophy. ROC analysis revealed the 78% accuracy, 71% sensitivity, and 85% specificity of the model, AUC = 0.82. According to our results, chronic low-grade inflammation and extracellular matrix remodeling are closely associated with the development of hypertrophy of EAT adipocytes, with serum concentrations of TNF-α, sPLA2 and CTX-I being the key predictors, describing the variability of epicardial adipocytes’ size.
Whole-Exome Sequencing Identified Rare Genetic Variants Associated with Undervirilized Genitalia in Taiwanese Pediatric Patients
Authors: Tsai Meng-Che , Weng Yun-Han , Lin Yu-Fang , Wang Yi-Chieh , Yu Hui-Wen , Chou Yen-Yin , Chen Peng-Chieh
Published: January 2023

Disorders/differences of sex development (DSDs) are a group of rare and phenotypically variable diseases. The underlying genetic causes of most cases of 46XY DSDs remains unknown. Despite the advent of genetic testing, current investigations of the causes of DSDs allow genetic-mechanism identification in about 20–35% of cases. This study aimed primarily to establish a rapid and high-throughput genetic test for undervirilized males with and without additional dysmorphic features. Routine chromosomal and endocrinological investigations were performed as part of DSD evaluation. We applied whole-exome sequencing (WES) complemented with multiplex ligation-dependent probe amplification to seek explainable genetic causes. Integrated computing programs were used to call and predict the functions of genetic variants. We recruited 20 patients and identified the genetic etiologies for 14 (70%) patients. A total of seven of the patients who presented isolated DSD phenotypes were found to have causative variants in the AR, MAP3K1, and FLNA genes. Moreover, the other seven patients presented additional phenotypes beyond undervirilized genitalia. Among them, two patients were compatible with CHARGE syndrome, one with Robinow syndrome, and another three with hypogonadotropic hypogonadism. One patient, who carried a heterozygous FLNA mutation, also harbored a heterozygous PTPN11 mutation and thus presented some phenotypes of Noonan syndrome. We identified several genetic variants (12 nonsense mutations and one microdeletion) that account for syndromic and nonsyndromic DSDs in the Taiwanese population. The identification of these causative genes extended our current understanding of sex development and related congenital disorders.
Enrichment of Bone Tissue with Antibacterially Effective Amounts of Nitric Oxide Derivatives by Treatment with Dielectric Barrier Discharge Plasmas Optimized for Nitrogen Oxide Chemistry
Authors: Feibel Dennis , Kwiatkowski Alexander , Opländer Christian , Grieb Gerrit , Windolf Joachim , Suschek Christoph V.
Published: January 2023

Cold atmospheric plasmas (CAPs) generated by dielectric barrier discharge (DBD), particularly those containing higher amounts of nitric oxide (NO) or NO derivates (NOD), are attracting increasing interest in medical fields. In the present study, we, for the first time, evaluated DBD-CAP-induced NOD accumulation and therapeutically relevant NO release in calcified bone tissue. This knowledge is of great importance for the development of new therapies against bacterial-infectious complications during bone healing, such as osteitis or osteomyelitis. We found that by modulating the power dissipation in the discharge, it is possible (1) to significantly increase the uptake of NODs in bone tissue, even into deeper regions, (2) to significantly decrease the pH in CAP-exposed bone tissue, (3) to induce a long-lasting and modulable NO production in the bone samples as well as (4) to significantly protect the treated bone tissue against bacterial contaminations, and to induce a strong bactericidal effect in bacterially infected bone samples. Our results strongly suggest that the current DBD technology opens up effective NO-based therapy options in the treatment of local bacterial infections of the bone tissue through the possibility of a targeted modulation of the NOD content in the generated CAPs.
Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis
Authors: Zhong Hongfei , Geng Rulin , Zhang Yu , Ding Jingwen , Liu Miao , Deng Shengfeng , Tu Qiuyun
Published: January 2023

Diabetes mellitus (DM) is known to be a risk factor for dementia, especially in the elderly population, and close associations between diabetes and Alzheimer disease (AD) have been determined. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are insulin-sensitising drugs. In addition to their anti-diabetic properties, their effectiveness in preventing and decreasing cognitive impairment are the most recent characteristics that have been studied. For this study, we conducted a systematic review and meta-analysis to critically analyse and evaluate the existing data on the effects of PPAR-γ agonist therapy on the cognitive status of patients. For this purpose, we first analysed both early intervention and later treatment with PPAR-γ agonists, according to the disease status. The involved studies indicated that early PPAR-γ agonist intervention is beneficial for patients and that high-dose PPAR-γ therapy may have a better clinical effect, especially in reversing the effects of cognitive impairment. Furthermore, the efficacy of pioglitazone (PIO) seems to be promising, particularly for patients with comorbid diabetes. PIO presented a better clinical curative effect and safety, compared with rosiglitazone (RSG). Thus, PPAR-γ agonists play an important role in the inflammatory response of AD or DM patients, and clinical therapeutics should focus more on relevant metabolic indices.
The Homogeneous Azorean Machado-Joseph Disease Cohort: Characterization and Contributions to Advances in Research
Authors: Lima Manuela , Raposo Mafalda , Ferreira Ana , Melo Ana Rosa Vieira , Pavão Sara , Medeiros Filipa , Teves Luís , Gonzalez Carlos , Lemos João , Pires Paula , Lopes Pedro , Valverde David , Gonzalez José , Kay Teresa , Vasconcelos João
Published: January 2023

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. MJD is characterized by late-onset progressive cerebellar ataxia associated with variable clinical findings, including pyramidal signs and a dystonic-rigid extrapyramidal syndrome. In the Portuguese archipelago of the Azores, the worldwide population cluster for this disorder (prevalence of 39 in 100,000 inhabitants), a cohort of MJD mutation carriers belonging to extensively studied pedigrees has been followed since the late 1990s. Studies of the homogeneous Azorean MJD cohort have been contributing crucial information to the natural history of this disease as well as allowing the identification of novel molecular biomarkers. Moreover, as interventional studies for this globally rare and yet untreatable disease are emerging, this cohort should be even more important for the recruitment of trial participants. In this paper, we profile the Azorean cohort of MJD carriers, constituted at baseline by 20 pre-ataxic carriers and 52 patients, which currently integrates the European spinocerebellar ataxia type 3/Machado-Joseph disease Initiative (ESMI), a large European longitudinal MJD cohort. Moreover, we summarize the main studies based on this cohort and highlight the contributions made to advances in MJD research. Knowledge of the profile of the Azorean MJD cohort is not only important in the context of emergent interventional trials but is also pertinent for the implementation of adequate interventional measures, constituting relevant information for Lay Associations and providing data to guide healthcare decision makers.
Occurrence, Role, and Challenges of MicroRNA in Human Breast Milk: A Scoping Review
Authors: Kondracka Adrianna , Gil-Kulik Paulina , Kondracki Bartosz , Frąszczak Karolina , Oniszczuk Anna , Rybak-Krzyszkowska Magda , Staniczek Jakub , Kwaśniewska Anna , Kocki Janusz
Published: January 2023

MicroRNAs are non-coding segments of RNA involved in the epigenetic modulation of various biological processes. Their occurrence in biological fluids, such as blood, saliva, tears, and breast milk, has drawn attention to their potential influence on health and disease development. Hundreds of microRNAs have been isolated from breast milk, yet the evidence on their function remains inconsistent and inconclusive. The rationale for the current scoping review is to map the evidence on the occurrence, characterization techniques, and functional roles of microRNAs in breast milk. The review of the sources of this evidence highlights the need to address methodological challenges to achieve future advances in understanding microRNAs in breast milk, particularly their role in conditions such as neoplasms. Nonetheless, remarkable progress has been made in characterizing the microRNA profiles of human breast milk.
Biological Evaluation of Zinc Phosphate Cement for Potential Bone Contact Applications
Authors: Kotha Arun K. , Nicholson John W. , Booth Samantha E.
Published: January 2023

Zinc phosphate cement is used in dentistry to lute crowns and bridges. So far, its biocompatibility for other applications has not been studied. This paper reports the biocompatibility of zinc phosphate towards MG63 cells, testing both the material (discs; 3 mm diameter × 1 mm thick) and leachate from the cement. Cell viability was determined using an MTT assay, and cytotoxicity from the effects of leachate, studied in triplicate. Microscopy (optical and scanning electron) determined the morphology and proliferation of cells attached to zinc phosphate. ICP-OES measured element release into leachate, and anti-microbial behaviour was determined against Streptococcus pyrogenes cultured on a Brain Heart Infusion agar using cement discs (3 mm diameter × 1 mm thick). Zones of inhibition were measured after 72 h. MG63 cells proliferated on zinc phosphate surfaces and retained their morphology. The cells were healthy and viable as shown by an MTT assay, both on cement and in leachate. High levels of phosphorus but low levels of zinc were released into leachate. The cement showed minimal antimicrobial activity against S. pyogenes, probably due to the long maturation times used. Zinc phosphate cement was found to be biocompatible towards MG63 cells, which indicates that it may be capable of use in bone contact applications.
Investigation of Platelet Apoptosis in Patients after Surgical Myocardial Revascularization
Authors: Sokolovskaya Alisa A. , Popov Mikhail A. , Sergeeva Ekaterina A. , Metelkin Arkadiy A. , Zybin Dmitry I. , Shumakov Dmitry V. , Kubatiev Aslan A.
Published: January 2023

Platelets are one of the main participants in vascular accidents in cases of coronary heart disease (CHD). In this study, we sought to detect platelet apoptosis in patients with coronary artery disease who underwent scheduled myocardial revascularization surgery. To identify apoptotic events, we analyzed phosphatidylserine (PS) expression on the surface of platelets and mitochondrial membrane potential (ΔΨm) by flow cytometry in two groups of 30 patients aged 45–60 years: Group 1—patients before myocardial revascularization surgery and group 2—patients after myocardial revascularization surgery. The control group consisted of 10 healthy volunteers aged 45–60 years. According to our data, the percentage levels of PS expression in patients greatly decreased after surgery. We confirmed platelet apoptosis by recording depolarization of ΔΨm in pre- and postoperative patients. ΔΨm readings were considerably improved after surgery. Our data indicated that the functional parameters of platelets in patients with coronary heart disease differed from the characteristics of platelets in patients who underwent myocardial revascularization, and from those of patients in a control group. Future studies of platelet phenotypic characteristics and platelet apoptosis biomarkers should greatly advance our understanding of the pathophysiology of coronary heart disease, and further promote the development of methods for predicting adverse outcomes after surgery.
Highly Sensitive Simultaneous Stripping Voltametric Detection of Zn2+, Cd2+ and Hg2+ by Bismuth Codeposition Procedure with Graphdiyne−Modified Electrode
Authors: Ai Yijing , Wang Lisi , Fu Wanting , Ye Xiang , Zhou Juan , Zhang Xiaoping , He Shuhai , Sun Wei
Published: January 2023

In this paper, graphdiyne (GDY)−modified glassy carbon electrode was prepared and further used for the sensitive and simultaneous detection of three target heavy metal ions of Zn2+, Cd2+ and Hg2+ by codeposition with Bi3+ in the mixture solution. GDY−modified electrodes exhibit a larger electrode area and abundant active sites, which is favorable for absorbing more metal ions. Bismuth has low toxicity and can form alloys with zinc, cadmium and mercury. Therefore, three kinds of heavy metal ions can be pre-concentrated with bismuth on the GDY−modified electrode surface, and the following stripping analysis results in high sensitivity and selectivity. By using differential pulse anodic stripping voltammetry, the detection ranges of Zn2+, Cd2+ and Hg2+ were from 2.0 to 100.0 μM with low detection limits of 0.255 μM, 0.367 μM and 0.796 μM, respectively. In addition, the sensor showed excellent repeatability, reproducibility, and stability, which was applied to sensitive analysis of river water samples with satisfactory results.
Senhance Robotic Platform in Pediatrics: Early US Experience
Authors: Puentes Maria Consuelo , Rojnica Marko , Sims Thomas , Jones Robert , Bianco Francesco M. , Lobe Thom E.
Published: January 2023

Introduction: Different robotic systems have been used widely in human surgery since 2000, but pediatric patients require some features that are lacking in the most frequently used robotic systems. Hypothesis: The Senhance® robotic system is a safe and an effective device for use in infants and children that has some advantages over other robotic systems. Methods: All patients between 0 and 18 years of age whose surgery was amenable to laparoscopy were offered enrollment in this IRB-approved study. We assessed the feasibility, ease and safety of using this robotic platform in pediatric patients including: set-up time, operative time, conversions, complications and outcomes. Results: Eight patients, ranging from 4 months to 17 years of age and weighing between 8 and 130 kg underwent a variety of procedures including: cholecystectomy (3), inguinal herniorrhaphy (3), orchidopexy for undescended testes (1) and exploration for a suspected enteric duplication cyst (1). All robotic procedures were successfully performed. The 4-month-old (mo), 8 kg patient underwent an uneventful robotic exploration in an attempt to locate a cyst that was hidden in the mesentery at the junction of the terminal ileum and cecum, but ultimately the patient required an anticipated laparotomy to palpate the cyst definitively and to excise it completely. There was no blood loss and no complications. Robotic manipulation with the reusable 3 mm instruments proved successful in all cases. Conclusions: Our initial experience with the Senhance® robotic platform suggests that this is a safe and effective device for pediatric surgery that is easy to use, and which warrants continued evaluation. Most importantly, there appears to be no lower age or weight restrictions to its use.