bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Different Basketball Shooting Positions and Distances on Gaze Behavior and Shooting Accuracy
Authors: Amaro Catarina M. , Amaro Ana M. , Gomes Beatriz B. , Castro Maria António , Mendes Rui
Published: February 2023

Basketball is a sport where in order to obtain points, it is necessary to put the ball in the basket. Therefore, basketball players need to shoot the ball accurately. This study aimed to evaluate if there are differences between shooting positions and angles concerning athlete visual behavior. Tobii Pro Glasses 3 was used to measure the number and duration of fixations in the target during shooting movement. The sample included 18 basketball players (10 female and 8 males; 22 ± 3.72 years; 12.5 ± 4.52 years of federated basketball practice) who performed a total of 60 shots in all shooting conditions and positions. Two distances (free throw and 3 points line) and three angles (45°, 90°, and 135°) in the 3 points shot were considered in all three shooting conditions (baseline, simulated opposition, and gym audience noise). Between distances, statistically significant differences occurred in the number and total duration of fixations and shooting accuracy. At a greater distance from the basket, the athlete tended to have less accuracy, as well as a lower number and duration of fixations. Between angles, there was no statistically significant differences, neither a tendency towards lower or higher values between them. Moreover, the shooting accuracy was better when the athlete focused for more time on the target, which occurred in the free throw condition.
Real-Time, Model-Agnostic and User-Driven Counterfactual Explanations Using Autoencoders
Authors: Labaien Soto Jokin , Zugasti Uriguen Ekhi , De Carlos Garcia Xabier
Published: February 2023

Explainable Artificial Intelligence (XAI) has gained significant attention in recent years due to concerns over the lack of interpretability of Deep Learning models, which hinders their decision-making processes. To address this issue, counterfactual explanations have been proposed to elucidate the reasoning behind a model’s decisions by providing what-if statements as explanations. However, generating counterfactuals traditionally involves solving an optimization problem for each input, making it impractical for real-time feedback. Moreover, counterfactuals must meet specific criteria, including being user-driven, causing minimal changes, and staying within the data distribution. To overcome these challenges, a novel model-agnostic approach called Real-Time Guided Counterfactual Explanations (RTGCEx) is proposed. This approach utilizes autoencoders to generate real-time counterfactual explanations that adhere to these criteria by optimizing a multiobjective loss function. The performance of RTGCEx has been evaluated on two datasets: MNIST and Gearbox, a synthetic time series dataset. The results demonstrate that RTGCEx outperforms traditional methods in terms of speed and efficacy on MNIST, while also effectively identifying and rectifying anomalies in the Gearbox dataset, highlighting its versatility across different scenarios.
Around Ruins: Some Notes on Feminist and Decolonial Conversations in Aesthetics
Authors: Oliveira Márcia
Published: February 2023

Although using different strategies, Portuguese artists Mónica de Miranda and Filipa César make us think about and reflect on the ruins of the Portuguese ‘empire’ but also on the ruins—and the remains—of European colonialism and its patriarchal backbone. Their work opens the possibility of discussing aesthetics from feminist and decolonial perspectives, departing from the category of ‘ruins’ and considering the many ways through which these ruins and their multiple inflections contribute to the creation of potential affective geographies and memories.
Response of Alhagi sparsifolia Seedlings to AMF Inoculation and Nitrogen Addition under Drought Stress
Authors: Aili Yilinuer , Chen Xiaonan , Gao Wenli , Wang Haiou , Dawuti Maigepiretiguli , Ma Xiaodong
Published: February 2023

Riparian forest veg etation in the lower Tarim River desert often faces a water and nitrogen deficiency. To investigate the ecological effects of drought stress and nitrogen limitation of arbuscular mycorrhizal fungi (AMF) on Alhagi sparsifolia seedlings at the vulnerable stage of growth, a control experiment was conducted on Alhagi sparsifolia seedlings with indoor potted plants. The main findings are as follows: drought stress inhibited the normal growth and development of Alhagi sparsifolia seedlings. When Alhagi sparsifolia seedlings were inoculated with AMF and at the N1 (50 mmol·L−1) nitrogen addition level, the mycorrhizal infection rate of Alhagi sparsifolia seedlings was the best: 84.44% under sufficient moisture content and 77.78% under drought stress. Under the same nitrogen treatment, the relative growth rate of Alhagi sparsifolia seedling height and base diameter, plant biomass, root system indicators (total root length, root surface area, root volume, average root diameter, the number of tips, and root shoot ratio), chlorophyll content (except for the chlorophyll a/b content at the N0 (0 mmol·L−1) nitrogen addition level), Fv/Fm, total nitrogen content, idole acetic acid (IAA) and gibberellic acid (GA) content were initially decreased, then increased and finally decreased again. Each of these indicators was increased significantly after being inoculated with AMF, and they reached their maximum value under the normal moisture and AMF treatment; however specific root length (except for at the N0 (0 mmol·L−1) nitrogen addition level), minimal fluorescence (Fo), antioxidant enzyme activity, the contents of osmotic regulation substances, abscisic acid (ABA) and strigolactones (SLs) contents were initially increased, then decreased and finally increased again, and they reached their maximum value under drought stress and AMF treatment. Under the same CK (black control), D (drought stress), CK + A (inoculated with AMF under black control), and D + A (inoculated with AMF under drought stress) treatments, all of the above indicators, except for specific root length, chlorophyll a/b content, minimal fluorescence (Fo), maximum fluorescence (Fm) and malondialdehyde (MDA) content initially increased and then decreased with the increasing nitrogen addition rate, and they reached the maximum value at the N1 (50 mmol·L−1) nitrogen addition level. Therefore, in the arid and N-deficient lower Tarim River region, Alhagi sparsifolia seedlings established an efficient symbiotic structure with AMF, which improved the drought resistance of seedlings and promoted the rapid passage of seedlings through the growth vulnerability period. This indicates that AMF inoculation is a key link in the survival strategy of Alhagi sparsifolia.
Turbulent Inflow Generation for Large-Eddy Simulation of Winds around Complex Terrain
Authors: Senocak Inanc , DeLeon Rey
Published: February 2023

Accurate turbulent inflow conditions are needed to broaden the application of the large-eddy simulation technique to predict winds around arbitrarily complex terrain. We investigate the concept of buoyancy perturbations with colored noise to trigger turbulence in upstream flows approaching complex terrain regions. Random perturbations are imposed on the source term in the pseudo-temperature transport equation. These perturbations are effective within three-dimensional boxes and scaled using a bulk Richardson number defined for each box. We apply the turbulent inflow generation technique to predict winds around the Askervein and Bolund Hills under neutrally stratified conditions. We find that a common value for the bulk Richardson number works well for a variety of flow problems. Additionally, we show that the height of the perturbation box plays an important role in the accuracy of the predictions around complex terrain. We consistently obtained good results for both simulation cases when the perturbation box height was made a fraction of the Obukhov length scale.
Assessment of Climate Indices over the Carpathian Basin Based on ALADIN5.2 and REMO2015 Regional Climate Model Simulations
Authors: Megyeri-Korotaj Otília A. , Bán Beatrix , Suga Réka , Allaga-Zsebeházi Gabriella , Szépszó Gabriella
Published: February 2023

The Hungarian Meteorological Service has been conducting climate model simulations in order to assess the effects of climate change in the Carpathian Basin and provide data for impact research and stakeholders. Two regional climate models are used: ALADIN-Climate 5.2 (hereafter ALADIN5.2) and REMO2015. They were tested for the past when the lateral boundary conditions were taken from two sources. ERA-Interim reanalysis was used in the evaluation experiment, while the CNRM-CM5 and the MPI-ESM-LR global climate models (GCM) provided the forcings in the control experiments. The model outputs were compared with the CarpatClim-HU observational dataset for the 1981–2000 period. Future projections were carried out with the RCP4.5 and RCP8.5 scenarios, and the results were analyzed for 2021–2050 and 2071–2100. The evaluation of the results focused mainly on climate indices calculated from temperature and precipitation. The validation results showed that REMO2015 assessed the mean temperature well, but the indices based on the minimum and maximum temperature had a significant bias which has to be taken into account when interpreting future changes. The model overestimated the minimum temperature in summer, which might affect the number of tropical nights. Moreover, the maximum temperature was underestimated; thus, the derived indices, such as the occurrence of summer days and hot days, were profoundly underestimated. In comparison, ALADIN5.2 had smaller biases for the high temperature indices; moreover, the number of hot days and extremely cold days was overestimated. Taking future projections into account, we can clearly see that the results of REMO2015 show a much more moderate increase in temperature than ALADIN5.2. The reasons are yet unknown and require further investigation. In spring and summer, the number of wet days was slightly overestimated, while the number of heavy precipitation days was marginally underestimated. The projections showed the highest uncertainty in the changes in mean summer precipitation and other precipitation indices. Although the REMO2015 model assessed a decrease in precipitation, ALADIN5.2 projected an increase in precipitation with a similar magnitude.
Aristotelian Diagrams for the Proportional Quantifier ‘Most’
Authors: Smessaert Hans , Demey Lorenz
Published: February 2023

In this paper, we study the interaction between the square of opposition for the Aristotelian quantifiers (‘all’, ‘some’, ‘no’, and ‘not all’) and the square of opposition generated by the proportional quantifier ‘most’ (in its standard generalized quantifier theory reading of ‘more than half’). In a first step, we provide an analysis in terms of bitstring semantics for the two squares independently. The classical square for ‘most’ involves a tripartition of logical space, whereas the degenerate square for ‘all’ in first-order logic (FOL) involves a quadripartition, due to FOL’s lack of existential import. In a second move, we combine these two squares into an octagon of opposition, which was hitherto unattested in logical geometry, while the meet of the original tri- and quadripartitions yields a hexapartition for this octagon. In a final step, we switch from FOL to a logical system, which does assume existential import. This yields an octagon of the well known Lenzen type, and its bitstring semantics is reduced to a pentapartition.
Long-Bone-Regeneration Process in a Sheep Animal Model, Using Hydroxyapatite Ceramics Prepared by Tape-Casting Method
Authors: Kresakova Lenka , Medvecky Lubomir , Vdoviakova Katarina , Varga Maros , Danko Ján , Totkovic Roman , Spakovska Tatiana , Vrzgula Marko , Giretova Maria , Briancin Jaroslav , Šimaiová Veronika , Kadasi Marian
Published: February 2023

This study was designed to investigate the effects of hydroxyapatite (HA) ceramic implants (HA cylinders, perforated HA plates, and nonperforated HA plates) on the healing of bone defects, addressing biocompatibility, biodegradability, osteoconductivity, osteoinductivity, and osteointegration with the surrounding bone tissue. The HA ceramic implants were prepared using the tape-casting method, which allows for shape variation in samples after packing HA paste into 3D-printed plastic forms. In vitro, the distribution and morphology of the MC3T3E1 cells grown on the test discs for 2 and 9 days were visualised with a fluorescent live/dead staining assay. The growth of the cell population was clearly visible on the entire ceramic surfaces and very good osteoblastic cell adhesion and proliferation was observed, with no dead cells detected. A sheep animal model was used to perform in vivo experiments with bone defects created on the metatarsal bones, where histological and immunohistochemical tissue analysis as well as X-ray and CT images were applied. After 6 months, all implants showed excellent biocompatibility with the surrounding bone tissue with no observed signs of inflammatory reaction. The histomorphological findings revealed bone growth immediately over and around the implants, indicating the excellent osteoconductivity of the HA ceramic implants. A number of islands of bone tissue were observed towards the centres of the HA cylinders. The highest degree of biodegradation, bioresorption, and new bone formation was observed in the group in which perforated HA plates were applied. The results of this study suggest that HA cylinders and HA plates may provide a promising material for the functional long-bone-defect reconstruction and further research.
Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine
Authors: Sebbagh Patrick , Cannone Alessandro , Gremion Gerald , Gremeaux Vincent , Raffoul Wassim , Hirt-Burri Nathalie , Michetti Murielle , Abdel-Sayed Philippe , Laurent Alexis , Wardé Nathalie , Applegate Lee Ann
Published: February 2023

Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions.
A Database of Lung Cancer-Related Genes for the Identification of Subtype-Specific Prognostic Biomarkers
Authors: Liu Yining , Zhao Min , Qu Hong
Published: February 2023

The molecular subtype is critical for accurate treatment and follow-up in patients with lung cancer; however, information regarding subtype-associated genes is dispersed among thousands of published studies. Systematic curation and cross-validation of the scientific literature would provide a solid foundation for comparative genetic studies of the major molecular subtypes of lung cancer. Here, we constructed a literature-based lung cancer gene database (LCGene). In the current release, we collected and curated 2507 unique human genes, including 2267 protein-coding and 240 non-coding genes from comprehensive manual examination of 10,960 PubMed article abstracts. Extensive annotations were added to aid identification of differentially expressed genes, potential gene editing sites, and non-coding gene regulation. For instance, we prepared 607 curated genes with CRISPR knockout information in 43 lung cancer cell lines. Further comparison of these implicated genes among different subtypes identified several subtype-specific genes with high mutational frequencies. Common tumor suppressors and oncogenes shared by lung adenocarcinoma and lung squamous cell carcinoma, for example, exhibited different mutational frequencies and prognostic features, suggesting the presence of subtype-specific biomarkers. Our retrospective analysis revealed 43 small cell lung cancer-specific genes. Moreover, 52 tumor suppressors and oncogenes shared by lung adenocarcinoma and squamous cell carcinoma confirmed the different molecular mechanisms of these two cancer subtypes. The subtype-based genetic differences, when combined, may provide insight into subtype-specific biomarkers for genetic testing.
Glycation Interferes with the Activity of the Bi-Functional UDP-N-Acetylglucosamine 2-Epimerase/N-Acetyl-mannosamine Kinase (GNE)
Authors: Hagenhaus Vanessa , Gorenflos López Jacob L. , Rosenstengel Rebecca , Neu Carolin , Hackenberger Christian P. R. , Celik Arif , Weinert Klara , Nguyen Mai-Binh , Bork Kaya , Horstkorte Rüdiger , Gesper Astrid
Published: February 2023

Mutations in the gene coding for the bi-functional UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme of the sialic acid biosynthesis, are responsible for autosomal-recessive GNE myopathy (GNEM). GNEM is an adult-onset disease with a yet unknown exact pathophysiology. Since the protein appears to work adequately for a certain period of time even though the mutation is already present, other effects appear to influence the onset and progression of the disease. In this study, we want to investigate whether the late onset of GNEM is based on an age-related effect, e.g., the accumulation of post-translational modifications (PTMs). Furthermore, we also want to investigate what effect on the enzyme activity such an accumulation would have. We will particularly focus on glycation, which is a PTM through non-enzymatic reactions between the carbonyl groups (e.g., of methylglyoxal (MGO) or glyoxal (GO)) with amino groups of proteins or other biomolecules. It is already known that the levels of both MGO and GO increase with age. For our investigations, we express each domain of the GNE separately, treat them with one of the glycation agents, and determine their activity. We demonstrate that the enzymatic activity of the N-acetylmannosamine kinase (GNE-kinase domain) decreases dramatically after glycation with MGO or GO—with a remaining activity of 13% ± 5% (5 mM MGO) and 22% ± 4% (5 mM GO). Whereas the activity of the UDP-N-acetylglucosamine 2-epimerase (GNE-epimerase domain) is only slightly reduced after glycation—with a remaining activity of 60% ± 8% (5 mM MGO) and 63% ± 5% (5 mM GO).
L-arginine and Its Derivatives Correlate with Exercise Capacity in Patients with Advanced Heart Failure
Authors: Drohomirecka Anna , Waś Joanna , Wiligórska Natalia , Rywik Tomasz M. , Komuda Krzysztof , Sokołowska Dorota , Lutyńska Anna , Zieliński Tomasz
Published: February 2023

Methylated arginine metabolites interrupt nitric oxide synthesis, which can result in endothelium dysfunction and inadequate vasodilation. Since little is known about the dynamics of arginine derivatives in patients with heart failure (HF) during physical exercise, we aimed to determine this as well as its impact on the patient outcomes. Fifty-one patients with HF (left ventricle ejection fraction-LVEF ≤ 35%, mean 21.7 ± 5.4%) underwent the cardiopulmonary exercise test (CPET). Plasma concentrations of L-arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured before and directly after CPET. All patients were followed for a mean of 23.5 ± 12.6 months. The combined endpoint was: any death, urgent heart transplantation, or urgent LVAD implantation. L-arginine concentrations increased significantly after CPET (p = 0.02), when ADMA (p = 0.01) and SDMA (p = 0.0005) decreased. The parameters of better exercise capacity were positively correlated with post-CPET concentration of L-arginine and inversely with post-CPET changes in ADMA, SDMA, and baseline and post-CPET SDMA concentrations. Baseline and post-CPET SDMA concentrations increased the risk of endpoint occurrence (HR 1.02, 95% CI 1.009–1.03, p = 0.04 and HR 1.02, 95% CI 1.01–1.03, p = 0.02, respectively). In conclusion, in patients with HF, extensive exercise is accompanied by changes in arginine derivatives that can reflect endothelium function. These observations may contribute to the explanation of the pathophysiology of exercise intolerance in HF.
Targeted and Suspect Fatty Acid Profiling of Royal Jelly by Liquid Chromatography—High Resolution Mass Spectrometry
Authors: Mantzourani Christiana , Kokotou Maroula G.
Published: February 2023

Royal jelly (RJ) is a bee product produced by the mandibular and hypopharyngeal glands of worker honeybees which has attracted special attention because of its numerous pharmacological activities and its applications to dermatology and cosmetics. In 2020, we demonstrated a liquid chromatography–high resolution mass spectrometry (LC–HRMS) method for the determination of seven medium-chain FFAs in RJ samples. The aim of the present work was to extend our studies on FA profiling of RJ, exploring the presence of common long-chain saturated, mono-unsaturated and poly-unsaturated free FAs in RJ samples using this LC–HRMS method. Among twenty common FAs studied by a targeted approach, palmitic acid, stearic acid and oleic acid were found at concentrations higher than the rest of the FAs (the concentrations of these three acids ranged from 37.4 to 48.0, from 17.7 to 24.0 and from 9.4 to 11.1 mg/100 g of fresh RJ, respectively). The high mass accuracy of LC–HRMS allowed the application of a suspect approach, which enabled the exploration of various C9 and C11 FAs, as well as hydroxylated C12 FAs. Nonenoic acid was indicated as the most abundant among these acids. In addition, for the first time, the presence of a variety of regio-isomers of hydroxymyristic, hydroxypalmitic and hydroxystearic acids was demonstrated in RJ samples.
Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation
Authors: Fonseca Óscar , Gomes Maria Salomé , Amorim Maria Adelina , Gomes Ana Cordeiro
Published: February 2023

Cystic fibrosis is a monogenic disease with a multisystemic phenotype, ranging from predisposition to chronic lung infection and inflammation to reduced bone mass. The exact mechanisms unbalancing the maintenance of an optimal bone mass in cystic fibrosis patients remain unknown. Multiple factors may contribute to severe bone mass reduction that, in turn, have devastating consequences in the patients’ quality of life and longevity. Here, we will review the existing evidence linking the CFTR dysfunction and cell-intrinsic bone defects. Additionally, we will also address how the proinflammatory environment due to CFTR dysfunction in immune cells and chronic infection impairs the maintenance of an adequate bone mass in CF patients.
Alterations in the Cellular Metabolic Footprint Induced by Mayaro Virus
Authors: Castro Ceyla M. O. , Mota Mânlio T. O. , Vidotto Alessandra , Caruso Ícaro P. , Ribeiro Milene R. , Moraes Fábio R. , Souza Fátima P. , Nogueira Mauricio L.
Published: February 2023

Mayaro virus is a neglected virus that causes a mild, dengue-like febrile syndrome characterized by fever, headache, rash, retro-orbital pain, vomiting, diarrhea, articular edemas, myalgia, and severe arthralgia, symptoms which may persist for months and become very debilitating. Though the virus is limited to forest areas and is most frequently transmitted by Haemagogus mosquitoes, Aedes mosquitoes can also transmit this virus and, therefore, it has the potential to spread to urban areas. This study focuses on the metabolic foot-printing of Vero cells infected with the Mayaro virus. Nuclear magnetic resonance combined with multivariate analytical methods and pattern recognition tools found that metabolic changes can be attributed to the effects of Mayaro virus infection on cell culture. The results suggest that several metabolite levels vary in infection conditions at different time points. There were important differences between the metabolic profile of non-infected and Mayaro-infected cells. These organic compounds are metabolites involved in the glycolysis pathway, the tricarboxylic acid cycle, the pentose phosphate pathway, and the oxidation pathway of fatty acids (via β-oxidation). This exometabolomic study has generated a biochemical profile reflecting the progressive cytopathological metabolic alterations induced by Mayaro virus replication in the cells and can contribute to the knowledge of the molecular mechanisms involved in viral pathogenesis.
Multi-Process Remora Enhanced Hyperparameters of Convolutional Neural Network for Lung Cancer Prediction
Authors: Appadurai Jothi Prabha , G Suganeshwari , Prabhu Kavin Balasubramanian , C Kavitha , Lai Wen-Cheng
Published: February 2023

In recent years, lung cancer prediction is an essential topic for reducing the death rate of humans. In the literature section, some papers are reviewed that reduce the accuracy level during the prediction stage. Hence, in this paper, we develop a Multi-Process Remora Optimized Hyperparameters of Convolutional Neural Network (MPROH-CNN) aimed at lung cancer prediction. The proposed technique can be utilized to detect the CT images of the human lung. The proposed technique proceeds with four phases, including pre-processing, feature extraction and classification. Initially, the databases are collected from the open-source system. After that, the collected CT images contain unwanted noise, which affects classification efficiency. So, the pre-processing techniques can be considered to remove unwanted noise from the input images, such as filtering and contrast enhancement. Following that, the essential features are extracted with the assistance of feature extraction techniques such as histogram, texture and wavelet. The extracted features are utilized to classification stage. The proposed classifier is a combination of the Remora Optimization Algorithm (ROA) and Convolutional Neural Network (CNN). In the CNN, the ROA is utilized for multi process optimization such as structure optimization and hyperparameter optimization. The proposed methodology is implemented in MATLAB and performances are evaluated by utilized performance matrices such as accuracy, precision, recall, specificity, sensitivity and F_Measure. To validate the projected approach, it is compared with the traditional techniques CNN, CNN-Particle Swarm Optimization (PSO) and CNN-Firefly Algorithm (FA), respectively. From the analysis, the proposed method achieved a 0.98 accuracy level in the lung cancer prediction.
Sample Size Analysis for Machine Learning Clinical Validation Studies
Authors: Goldenholz Daniel M. , Sun Haoqi , Ganglberger Wolfgang , Westover M. Brandon
Published: February 2023

Background: Before integrating new machine learning (ML) into clinical practice, algorithms must undergo validation. Validation studies require sample size estimates. Unlike hypothesis testing studies seeking a p-value, the goal of validating predictive models is obtaining estimates of model performance. There is no standard tool for determining sample size estimates for clinical validation studies for machine learning models. Methods: Our open-source method, Sample Size Analysis for Machine Learning (SSAML) was described and was tested in three previously published models: brain age to predict mortality (Cox Proportional Hazard), COVID hospitalization risk prediction (ordinal regression), and seizure risk forecasting (deep learning). Results: Minimum sample sizes were obtained in each dataset using standardized criteria. Discussion: SSAML provides a formal expectation of precision and accuracy at a desired confidence level. SSAML is open-source and agnostic to data type and ML model. It can be used for clinical validation studies of ML models.
The Roles of Glutamate Receptors and Their Antagonists in Status Epilepticus, Refractory Status Epilepticus, and Super-Refractory Status Epilepticus
Authors: Huang Tzu-Hsin , Lai Ming-Chi , Chen Yu-Shiue , Huang Chin-Wei
Published: February 2023

Status epilepticus (SE) is a neurological emergency with a high mortality rate. When compared to chronic epilepsy, it is distinguished by the durability of seizures and frequent resistance to benzodiazepine (BZD). The Receptor Trafficking Hypothesis, which suggests that the downregulation of γ-Aminobutyric acid type A (GABAA) receptors, and upregulation of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play major roles in the establishment of SE is the most widely accepted hypothesis underlying BZD resistance. NMDA and AMPA are ionotropic glutamate receptor families that have important excitatory roles in the central nervous system (CNS). They are both essential in maintaining the normal function of the brain and are involved in a variety of neuropsychiatric diseases, including epilepsy. Based on animal and human studies, antagonists of NMDA and AMPA receptors have a significant impact in ending SE; albeit most of them are not yet approved to be in clinically therapeutic guidelines, due to their psychomimetic adverse effects. Although there is still a dearth of randomized, prospective research, NMDA antagonists such as ketamine, magnesium sulfate, and the AMPA antagonist, perampanel, are regarded to be reasonable optional adjuvant therapies in controlling SE, refractory SE (RSE) or super-refractory SE (SRSE), though there are still a lack of randomized, prospective studies. This review seeks to summarize and update knowledge on the SE development hypothesis, as well as clinical trials using NMDA and AMPA antagonists in animal and human studies of SE investigations.
MiRNAs Action and Impact on Mitochondria Function, Metabolic Reprogramming and Chemoresistance of Cancer Cells: A Systematic Review
Authors: Rosolen Daiane , Nunes-Souza Emanuelle , Marchi Rafael , Tofolo Maria Vitoria , Antunes Valquíria C. , Berti Fernanda C. B. , Fonseca Aline S. , Cavalli Luciane R.
Published: February 2023

MicroRNAs (miRNAs) are involved in the regulation of mitochondrial function and homeostasis, and in the modulation of cell metabolism, by targeting known oncogenes and tumor suppressor genes of metabolic-related signaling pathways involved in the hallmarks of cancer. This systematic review focuses on articles describing the role, association, and/or involvement of miRNAs in regulating the mitochondrial function and metabolic reprogramming of cancer cells. Following the PRISMA guidelines, the articles reviewed were published from January 2010 to September 2022, with the search terms “mitochondrial microRNA” and its synonyms (mitochondrial microRNA, mitochondrial miRNA, mito microRNA, or mitomiR), “reprogramming metabolism,” and “cancer” in the title or abstract). Thirty-six original research articles were selected, revealing 51 miRNAs with altered expression in 12 cancers: bladder, breast, cervical, colon, colorectal, liver, lung, melanoma, osteosarcoma, pancreatic, prostate, and tongue. The actions of miRNAs and their corresponding target genes have been reported mainly in cell metabolic processes, mitochondrial dynamics, mitophagy, apoptosis, redox signaling, and resistance to chemotherapeutic agents. Altogether, these studies support the role of miRNAs in the metabolic reprogramming hallmark of cancer cells and highlight their potential as predictive molecular markers of treatment response and/or targets that can be used for therapeutic intervention.
Surface Micro-Patterned Biofunctionalized Hydrogel for Direct Nucleic Acid Hybridization Detection
Authors: Zezza Paola , Lucío María Isabel , Fernández Estrella , Maquieira Ángel , Bañuls María-José
Published: February 2023

The present research is focused on the development of a biofunctionalized hydrogel with a surface diffractive micropattern as a label-free biosensing platform. The biosensors described in this paper were fabricated with a holographic recording of polyethylene terephthalate (PET) surface micro-structures, which were then transferred into a hydrogel material. Acrylamide-based hydrogels were obtained with free radical polymerization, and propargyl acrylate was added as a comonomer, which allowed for covalent immobilization of thiolated oligonucleotide probes into the hydrogel network, via thiol-yne photoclick chemistry. The comonomer was shown to significantly contribute to the immobilization of the probes based on fluorescence imaging. Two different immobilization approaches were demonstrated: during or after hydrogel synthesis. The second approach showed better loading capacity of the bioreceptor groups. Diffraction efficiency measurements of hydrogel gratings at 532 nm showed a selective response reaching a limit of detection in the complementary DNA strand of 2.47 µM. The label-free biosensor as designed could significantly contribute to direct and accurate analysis in medical diagnosis as it is cheap, easy to fabricate, and works without the need for further reagents.
Nucleic Acid Quantification by Multi-Frequency Impedance Cytometry and Machine Learning
Authors: Kokabi Mahtab , Sui Jianye , Gandotra Neeru , Pournadali Khamseh Arastou , Scharfe Curt , Javanmard Mehdi
Published: February 2023

Determining nucleic acid concentrations in a sample is an important step prior to proceeding with downstream analysis in molecular diagnostics. Given the need for testing DNA amounts and its purity in many samples, including in samples with very small input DNA, there is utility of novel machine learning approaches for accurate and high-throughput DNA quantification. Here, we demonstrated the ability of a neural network to predict DNA amounts coupled to paramagnetic beads. To this end, a custom-made microfluidic chip is applied to detect DNA molecules bound to beads by measuring the impedance peak response (IPR) at multiple frequencies. We leveraged electrical measurements including the frequency and imaginary and real parts of the peak intensity within a microfluidic channel as the input of deep learning models to predict DNA concentration. Specifically, 10 different deep learning architectures are examined. The results of the proposed regression model indicate that an R_Squared of 97% with a slope of 0.68 is achievable. Consequently, machine learning models can be a suitable, fast, and accurate method to measure nucleic acid concentration in a sample. The results presented in this study demonstrate the ability of the proposed neural network to use the information embedded in raw impedance data to predict the amount of DNA concentration.
Network-Based Differences in Top–Down Multisensory Integration between Adult ADHD and Healthy Controls—A Diffusion MRI Study
Authors: Schulze Marcel , Aslan Behrem , Farrher Ezequiel , Grinberg Farida , Shah Nadim , Schirmer Markus , Radbruch Alexander , Stöcker Tony , Lux Silke , Philipsen Alexandra
Published: February 2023

Background: Attention-deficit–hyperactivity disorder (ADHD) is a neurodevelopmental disorder neurobiologically conceptualized as a network disorder in white and gray matter. A relatively new branch in ADHD research is sensory processing. Here, altered sensory processing i.e., sensory hypersensitivity, is reported, especially in the auditory domain. However, our perception is driven by a complex interplay across different sensory modalities. Our brain is specialized in binding those different sensory modalities to a unified percept—a process called multisensory integration (MI) that is mediated through fronto-temporal and fronto-parietal networks. MI has been recently described to be impaired for complex stimuli in adult patients with ADHD. The current study relates MI in adult ADHD with diffusion-weighted imaging. Connectome-based and graph-theoretic analysis was applied to investigate a possible relationship between the ability to integrate multimodal input and network-based ADHD pathophysiology. Methods: Multishell, high-angular resolution diffusion-weighted imaging was performed on twenty-five patients with ADHD (six females, age: 30.08 (SD: 9.3) years) and twenty-four healthy controls (nine females; age: 26.88 (SD: 6.3) years). Structural connectome was created and graph theory was applied to investigate ADHD pathophysiology. Additionally, MI scores, i.e., the percentage of successful multisensory integration derived from the McGurk paradigm, were groupwise correlated with the structural connectome. Results: Structural connectivity was elevated in patients with ADHD in network hubs mirroring altered default-mode network activity typically reported for patients with ADHD. Compared to controls, MI was associated with higher connectivity in ADHD between Heschl’s gyrus and auditory parabelt regions along with altered fronto-temporal network integrity. Conclusion: Alterations in structural network integrity in adult ADHD can be extended to multisensory behavior. MI and the respective network integration in ADHD might represent the maturational cortical delay that extends to adulthood with respect to sensory processing.
THINC-Integrated Tool (THINC-it): A Brief Measurement of Changes in Cognitive Functioning and Its Correlation with the Life Quality of Patients with Schizophrenia and Related Disorders—A Pilot Study
Authors: Szmyd Joanna K. , Lewczuk Karol , Teopiz Kayla M. , McIntyre Roger S. , Wichniak Adam
Published: February 2023

Background: This pilot study aimed to assess patients’ cognitive functioning with the Polish version of the THINC-it tool and to analyze its association with self-reported quality of life (QOL). Methods: Twenty-one patients (mean age: 37.8 ± 10.4) were assessed at baseline and after six weeks of a standard therapeutic outpatient program. Participants completed the World Health Organization QOL Questionnaire (WHOQOL-BREF) and the THINC-it tool at both visits. The tool consists of tasks evaluating working memory (SYMBOL CHECK), attention (SPOTTER), executive functions (TRIALS), and cognitive skills (CODEBREAKER). Results: During the second visit, patients showed significant improvements in mean latency of correct responses of SPOTTER: p = 0.021, Cohen’s d = 0.38 and in the Physical health domain: p = 0.007, Cohen’s d = 0.37. The number of correct responses for CODEBREAKER was positively associated with the Physical health domain at visit 1 (r = 0.53, p = 0.014) and visit 2 (r = 0.42, p = 0.058). The number of correct responses at SYMBOL CHECK was positively related to QOL in the Environment domain only at visit 2 (r = 0.45, p = 0.042). Conclusions: These results suggest the THINC-it tool has utility as a cognitive measure in adults with schizophrenia in both clinical and research settings.
Assessing Orofacial Pain Behaviors in Animal Models: A Review
Authors: Liu Sufang , Crawford Joshua , Tao Feng
Published: February 2023

Orofacial pain refers to pain occurring in the head and face, which is highly prevalent and represents a challenge to clinicians, but its underlying mechanisms are not fully understood, and more studies using animal models are urgently needed. Currently, there are different assessment methods for analyzing orofacial pain behaviors in animal models. In order to minimize the number of animals used and maximize animal welfare, selecting appropriate assessment methods can avoid repeated testing and improve the reliability and accuracy of research data. Here, we summarize different methods for assessing spontaneous pain, evoked pain, and relevant accompanying dysfunction, and discuss their advantages and disadvantages. While the behaviors of orofacial pain in rodents are not exactly equivalent to the symptoms displayed in patients with orofacial pain, animal models and pain behavioral assessments have advanced our understanding of the pathogenesis of such pain.
Diffusion Measures of Subcortical Structures Using High-Field MRI
Authors: Baek Hyeon-Man
Published: February 2023

The pathology of Parkinson’s disease (PD) involves the death of dopaminergic neurons in the substantia nigra (SN), which slowly influences downstream basal ganglia pathways as dopamine transport diminishes. Diffusion magnetic resonance imaging (MRI) has been used to diagnose PD by assessing white matter connectivity in some brain areas. For this study, we applied Lead-DBS to human connectome project data to automatically segment 11 subcortical structures of 49 human connectome project subjects, reducing the reliance on manual segmentation for more consistency. The Lead-connectome pipeline, which utilizes DSI Studio to generate structural connectomes from each 3T and 7T diffusion image, was applied to 3T and 7T data to investigate possible differences in diffusion measures due to different acquisition protocols. Significantly higher fractional anisotropy (FA) values were found in the 3T left SN; significantly higher MD values were found in the 3T left SN and the right amygdala, SN, and subthalamic nucleus (STN); significantly higher AD values were found in the right RN and STN; and significantly higher RD values were found in the left RN and right amygdala. We illustrate a methodology for obtaining diffusion measures of basal ganglia and basal ganglia connectivity using diffusion images, as well as show possible differences in diffusion measures that can arise due to the differences in MRI acquisitions.
The Effects of Language Teaching Pedagogy on Cognitive Functioning in Older Adults
Authors: van der Ploeg Mara , Lowie Wander , Keijzer Merel
Published: February 2023

With the field of late-life language learning (LLLL) expanding fast, ample attention has been paid to cognitive benefits ensuing from LLLL. However, these studies have yielded mixed results, which may be partly explained by seniors’ language learning needs not being taken into account, and theoretical insights on effective language teaching have not included seniors. In order to link seniors’ language learning needs to possible cognitive benefits, and to expand the second language acquisition literature, 16 Dutch seniors took part in a three-month English course, with or without explicit grammar instruction, to ascertain the effects of more implicit versus more explicit language teaching pedagogies on cognitive flexibility. More specifically, we used linear mixed effects models to determine these methods’ differential effects on attention, working memory, processing and switching speed, inhibition, and shifting and switching abilities, as subdomains of cognitive flexibility, by using a pretest–post-test–retention test design. On the digit span tasks, the explicitly taught group showed significant improvements compared to the implicitly taught group. For Dutch verbal fluency, participants’ performance significantly improved regardless of condition. On the other measures, no differences between the groups were found. Hence, if the goal is to improve seniors’ working memory, then explicit language instruction appears more fruitful than implicit language instruction.
Integration of BIM and Chinese Architectural Heritage: A Bibliometric Analysis Research
Authors: Ding Jianming , Liang Mingjie , Chen Wei
Published: February 2023

The research on the application of BIM technology in architectural heritage is increasing. Building information modeling (BIM) makes the realization of architectural heritage assessment, design, and management systematic and effective. However, little is known about the use of China-based BIM in conjunction with architectural heritage. Therefore, this study conducted a systematic literature analysis to determine the application fields and development trends of BIM and architectural heritage research in China. A total of 186 articles were retrieved from CNKI, of which 167 met the inclusion criteria and formed the basis of this systematic literature analysis. With the aid of the literature research visualization analysis software VOSviewer and SATI, a comprehensive literature visualization analysis was carried out. It was determined that the hot fields of BIM research in architectural heritage in China are mainly focused on (a) the perspective of data acquisition and measurement technology, (b) the perspective of model construction based on point cloud data acquisition, and (c) the perspective of BIM model application. Future research trends may focus on the information research of architectural heritage, combined with the application of BIM technology in the whole life cycle management of architectural heritage and other aspects.
Seismic Retrofitting of Mid-Rise Unreinforced Masonry Residential Buildings after the 2010 Kraljevo, Serbia Earthquake: A Case Study
Authors: Blagojević Predrag , Brzev Svetlana , Cvetković Radovan
Published: February 2023

There is a significant building stock of post-WWII low- and mid-rise unreinforced masonry (URM) buildings in Serbia and the region (former Yugoslavia). Numerous buildings of this typology collapsed due to the devastating 1963 Skopje, Yugoslavia earthquake, causing fatalities, injuries, and property losses, as well as experienced damage in a few recent earthquakes in the region, including the 2010 Kraljevo, Serbia earthquake (MW 5.5) and the 2020 Petrinja, Croatia earthquake (M 6.4). These buildings are three- to five-stories high, have clay brick masonry walls, and rigid floor slabs, usually with an RC ring beam at each floor level. This paper presents a case study of a URM building which was damaged due to the 2010 Kraljevo earthquake and subsequently retrofitted. A comparison of seismic analysis results, including the capacity/demand ratio and displacement/drift values, for the original and retrofitted building according to the seismic design and retrofit codes which were followed in Serbia as well as some of the neighboring countries for several decades and Eurocode 8 has been presented. The results of this study show that the selected retrofit solution that satisfied the Yugoslav seismic code requirements is not adequate according to the Eurocode 8, primarily due to significantly higher seismic demand.