bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Combination of Convolutional Neural Network and LightGBM Algorithm for Lung Cancer Histopathology Classification
Authors: Hamed Esraa A.-R. , Salem Mohammed A.-M. , Badr Nagwa L. , Tolba Mohamed F.
Published: July 2023

The most dangerous disease in recent decades is lung cancer. The most accurate method of cancer diagnosis, according to research, is through the use of histopathological images that are acquired by a biopsy. Deep learning techniques have achieved success in bioinformatics, particularly medical imaging. In this paper, we present an innovative method for rapidly identifying and classifying histopathology images of lung tissues by combining a newly proposed Convolutional Neural Networks (CNN) model with a few total parameters and the enhanced Light Gradient Boosting Model (LightGBM) classifier. After the images have been pre-processed in this study, the proposed CNN technique is provided for feature extraction. Then, the LightGBM model with multiple threads has been used for lung tissue classification. The simulation result, applied to the LC25000 dataset, demonstrated that the novel technique successfully classifies lung tissue with 99.6% accuracy and sensitivity. Furthermore, the proposed CNN model has achieved the lowest training parameters of only one million parameters, and it has also achieved the shortest processing time of just one second throughout the feature extraction process. When this result is compared with the most recent state-of-the-art approaches, the suggested approach has increased effectiveness in the areas of both disease classification accuracy and processing time.
Evaluation of Paxillin Expression in Epithelial Dysplasia, Oral Squamous Cell Carcinoma, Lichen Planus with and without Dysplasia, and Hyperkeratosis: A Retrospective Cross-Sectional Study
Authors: Aghili Seyedeh Sara , Zare Razieh , Jahangirnia Alireza
Published: July 2023

Background: Paxillin is a cytoskeletal protein involved in the pathogenesis of several types of cancers. However, the roles of paxillin in epithelial dysplasia (ED), oral squamous cell carcinoma (OSCC), oral lichen planus with dysplasia (OLPD), hyperkeratosis (HK), and oral lichen planus (OLP) have remained unnoticed in the literature. This study aimed to evaluate its attainable functions in the pathogenesis and malignant transformation of potentially malignant oral epithelium and benign lesions. Methods: In this retrospective cross-sectional study, paxillin expression was investigated in 99 tissue samples, including 18 cases of OSCC, 21 ED, 23 OLP, 21 OLPD, and 16 cases of HK. The tissue sections also underwent immunohistochemical paxillin staining using 3,3-diaminobenzidine (DAB) chromogen. The intensity, location, and percentage of staining were examined across all groups. Data were analyzed using the Shapiro–Wilk test, ANOVA, Pearson chi-square, Kruskal–Wallis, and Dunn’s post hoc test. Results: The cytoplasmic percentage and intensity staining of Paxillin expression were evident in the central/suprabasal and basal/peripheral layers of all the obtained samples. The final staining score was significantly higher in OSCC and dysplasia compared to HK and OLP (p = 0.004). It was found that paxillin expression is associated with the grade of dysplastic samples (p < 0.001). Conclusion: The present study provides evidence that paxillin may be involved in the pathogenesis of OSCC and the development and progression of dysplastic tissue, since the paxillin expression was higher than that of HK and OLP.
Research on Drone Fault Detection Based on Failure Mode Databases
Authors: Hou Defei , Su Qingran , Song Yi , Yin Yongfeng
Published: July 2023

Drones are widely used in a number of key fields and are having a profound impact on all walks of life. Working out how to improve drone safety through fault detection is key to ensuring the smooth execution of tasks. At present, most research focuses on fault detection at the component level as it is not possible to locate faults quickly from the global system state of a UAV. Moreover, most methods are offline detection methods, which cannot achieve real-time monitoring of UAV faults. To remedy this, this paper proposes a fault detection method based on a fault mode database and runtime verification. Firstly, a large body of historical fault information is analyzed to generate a summary of fault modes, including fault modes at the system level. The key safety properties of UAVs during operation are further studied in terms of system-level fault modes. Next, a monitor generation algorithm and code instrumentation framework are designed to monitor whether a certain safety attribute is violated during the operation of a UAV in real time. The experimental results show that the fault detection method proposed in this paper can detect abnormal situations in a timely and accurate manner.
Fractional Encoding of At-Most-K Constraints on SAT
Authors: Yonekura Miki , Nishimura Shunji
Published: July 2023

The satisfiability problem (SAT) in propositional logic determines if there is an assignment of values that makes a given propositional formula true. Recently, fast SAT solvers have been developed, and SAT encoding research has gained attention. This enables various real-world problems to be transformed into SAT and solved, realizing a solution to the original problems. We propose a new encoding method, Fractional Encoding, which focuses on the At-Most-K constraints—a bottleneck of computational complexity—and reduces the scale of logical expressions by dividing target variables. Furthermore, we confirm that Fractional Encoding outperforms existing methods in terms of the number of generated clauses and required auxiliary variables. Hence, it enables the efficient solving of real-world problems like planning and hardware verification.
Denying Evolution Resampling: An Improved Method for Feature Selection on Imbalanced Data
Authors: Quan Li , Gong Tao , Jiang Kaida
Published: July 2023

Imbalanced data classification is an important problem in the field of computer science. Traditional classification algorithms often experience a decrease in accuracy when the data distribution is uneven. Therefore, measures need to be taken to improve the balance of the dataset and enhance the classification accuracy of the model. We have designed a data resampling method to improve the accuracy of classification detection. This method relies on the negative selection process to constrain the data evolution process. By combining the CRITIC method with regression coefficients, we establish crossover selection probabilities for elite genes to achieve an evolutionary resampling process. Based on independent weights, the feature analysis improves by 3%. We evaluated the resampled results on publicly available datasets using traditional logistic regression with cross-validation. Compared to the other resampling models, the F1 score performance of the logistic regression five-fold cross-validation is more stable than the other methods using the two sampling results of the proposed method. The effectiveness of the proposed method is verified based on F1 score evaluation results.
An Alternative Regulation of Compensation Mechanisms for Electric Energy Transgressions of Service Quality Limits in Dispersed and Seasonal Areas
Authors: de Bitencourt Julio , Bernardon Daniel , Eichkoff Henrique , Garcia Vinicius , Silva Daiana , Chiara Lucas , Gomes Renan , Butto Sebastian , Barbosa Solange , Pose Alejandre
Published: July 2023

The evaluation of the quality of electric power distribution services in Brazil is regulated and monitored by the National Electric Energy Agency ANEEL, which uses metrics related to the duration frequency of power interruptions that occur in the power utilities’ networks. The methodology applied by the agency to establish financial compensation due to violations of the quality standards does not take into consideration the consumers’ production industry when establishing compensation for the transgression of service quality indicators. This study will analyze a case study of a group of industrial consumers linked to agribusiness in the southern region of Brazil, which have strongly seasonal use of distribution networks and are scattered in large, dispersed areas. Based on the evaluation of the impact of service quality indicators on financial compensation, a regulatory mechanism is proposed in the form of an interruptible tariff duly quantified in the form of a non-linear programming problem to find a discount range for uninterruptible tariffs. The results obtained with the real data for the group of irrigating consumers demonstrate the feasibility regarding the application of the proposed approach, whether due to the discounts offered or even the repercussions of the calculated financial amounts.
A Distributed Control Scheme for Cyber-Physical DC Microgrid Systems
Authors: Onaolapo Adeniyi K. , Sharma Gulshan , Bokoro Pitshou N. , Aluko Anuoluwapo , Pau Giovanni
Published: July 2023

An innovative distributed secondary control technique for balanced current sharing and voltage regulation for an off-grid DC microgrid setup is presented in this research. The droop control scheme is conventionally used for current sharing amongst distributed sources (DSs) in a microgrid. However, this method has two major drawbacks. Firstly, due to the line resistance of each DS, the output voltage is different for each DS, and the output current-sharing property deteriorates. Secondly, the droop action increases the DC bus voltage variation. To address these drawbacks, a fuzzy-based distributed secondary controller is proposed. The proposed controller in each DS simultaneously ensures balanced current sharing and sustains DC bus voltage at the reference value by using a communication network to interact with one another. The required circumstance to guarantee the proposed controller’s stability is provided. The stability analysis is beneficial to inform the choice of control parameters. The real-time simulation outputs demonstrate the proposed control scheme’s robustness in achieving the control objectives under varying operating conditions.
Stator ITSC Fault Diagnosis of EMU Asynchronous Traction Motor Based on apFFT Time-Shift Phase Difference Spectrum Correction and SVM
Authors: Ma Jie , Liu Xiaodong , Hu Jisheng , Fei Jiyou , Zhao Geng , Zhu Zhonghuan
Published: July 2023

EMU (electric multiple unit) traction motors are powered by converters whose output voltage increases the voltage stress borne by the insulation system, making the ITSC (inter-turn short-circuit) fault more prominent. An index based on short-circuit thermal power is proposed in the article to evaluate the non-metallic ITSC faults extent. The apFFT (all-phase FFT) time-shift phase difference correction with double Hanning windows is used to calculate fault features to train the SVM (support vector machine) fault diagnosis model whose hyper-parameters C and g are optimized using grid search methods. The experimental verification was carried out on the EMU electric traction simulation experimental platform. According to the fault extent index proposed in this article, the experimental samples were divided into three categories, normal, incipient and serious fault samples. The ITSC fault diagnosis accuracy was 100% on the training dataset and 93.33% on the test dataset. There was no misclassification between normal and serious ITSC fault samples.
Secure and Efficient Communication in Smart Grids
Authors: Fouda Mostafa M. , Ibrahem Mohamed I.
Published: July 2023

This Special Issue on “Secure and Efficient Communication in Smart Grids” received a total of 11 submitted articles, of which 5 were accepted and published after each passing an independent peer-review process [...]
Experimental Investigation of the Fractal-Permeability Properties of Locally Fractured Coal Bodies around Gas Extraction Boreholes
Authors: Pang Mingkun , Pan Hongyu , Zhu Shipeng , Zhang Yao , Zhang Tianjun
Published: July 2023

To investigate the permeability characteristics in the in-situ fractured coal body around the perimeter of gas extraction boreholes, the steady-state permeability of fractured coal bodies with different gradations was tested using the fractured rock permeability test system. By controlling the axial displacement and permeability pressure, the permeability parameters were obtained under different porosities. The interactions between the permeability parameters and the process of permeability destabilisation are discussed. The results show that the permeability characteristics of the broken coal body obey the Forchheimer relationship: As the axial displacement increases, the permeability resistance of the fluid increases and the non-Darcy property of the sample becomes more significant. With the decrease in the porosity of the sample and the increase in the power index n, the permeability k decreases and the non-Darcy factor β increases. The final fractal structure of the sample will be changed by particle fragmentation and migration during the loading process of the sample with different levels, and the internal pore structure of the sample will further affect the penetration of the penetration channel. A critical characteristic value for the seepage instability in broken coal bodies is given, and an expression for determining the seepage instability by permeability and non-Darcy factors is proposed. The results indicate that a negative non-Darcy factor is not a necessary condition for permeability instability, and the critical Reynolds number for the permeability instability in broken coal bodies was determined from the perspective of the Reynolds number. The conclusions of this study can provide theoretical support for the theoretical study of permeability and the permeability of pre-smoking coal seams.
Selection and Evaluation of Reference Genes for RT-qPCR Analysis in Amorphophallus Konjac Based on Transcriptome Data
Authors: Liu Yanli , Zhang Chengcheng , Harijati Nunung , Diao Ying , Liu Erxi , Hu Zhongli
Published: July 2023

Combined with the Konjac transcriptome database of our laboratory and internal reference genes commonly used in plants, the eight candidate internal reference genes were screened and detected. They are the 25S ribosomal RNA gene (25S rRNA), 18S ribosomal RNA gene (18S rRNA), actin gene (ACT), glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH), ubiquitin gene (UBQ), β-tubulin gene (β-TUB), eukaryotic elongation factor 1-αgene(eEF-1α), and eukaryotic translation initiation factor 4α-1 gene (eIF-4α). The results of GeNorm, Normfinder, and BestKeeper were analyzed comprehensively. The data showed that the expression levels of 25S rRNA, 18S rRNA, and ACT at the reproductive periods, eEF-1α and eIF-4α at the nutritional periods, and eEF-1α, UBQ, and ACT at different leaf developmental periods were stable. These identified and stable internal reference genes will provide the basis for the subsequent molecular biology-related studies of Konjac.
yaaJ, the tRNA-Specific Adenosine Deaminase, Is Dispensable in Bacillus subtilis
Authors: Soma Akiko , Kubota Atsushi , Tomoe Daisuke , Ikeuchi Yoshiho , Kawamura Fujio , Arimoto Hijiri , Shiwa Yuh , Kanesaki Yu , Nanamiya Hideaki , Yoshikawa Hirofumi , Suzuki Tsutomu , Sekine Yasuhiko
Published: July 2023

Post-transcriptional modifications of tRNA are crucial for their core function. The inosine (I; 6-deaminated adenosine) at the first position in the anticodon of tRNAArg(ICG) modulates the decoding capability and is generally considered essential for reading CGU, CGC, and CGA codons in eubacteria. We report here that the Bacillus subtilis yaaJ gene encodes tRNA-specific adenosine deaminase and is non-essential for viability. A β−galactosidase reporter assay revealed that the translational activity of CGN codons was not impaired in the yaaJ-deletion mutant. Furthermore, tRNAArg(CCG) responsible for decoding the CGG codon was dispensable, even in the presence or absence of yaaJ. These results strongly suggest that tRNAArg with either the anticodon ICG or ACG has an intrinsic ability to recognize all four CGN codons, providing a fundamental concept of non-canonical wobbling mediated by adenosine and inosine nucleotides in the anticodon. This is the first example of the four-way wobbling by inosine nucleotide in bacterial cells. On the other hand, the absence of inosine modification induced +1 frameshifting, especially at the CGA codon. Additionally, the yaaJ deletion affected growth and competency. Therefore, the inosine modification is beneficial for translational fidelity and proper growth-phase control, and that is why yaaJ has been actually conserved in B. subtilis.
Extracellular Vesicles Derived from Mesenchymal Stem Cells Promote Wound Healing and Skin Regeneration by Modulating Multiple Cellular Changes: A Brief Review
Authors: Zhang Weiyuan , Ling Yang , Sun Yang , Xiao Fengjun , Wang Lisheng
Published: July 2023

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are biologically active substances secreted by MSCs into the extracellular matrix that play an immunomodulatory role in skin damage repair. To investigate the mechanism of MSC-EVs in reducing inflammation, promoting angiogenesis, promoting the proliferation and migration of epithelial cells and fibroblasts, and extracellular matrix remodeling during wound healing, we focused on the effects of EVs on multiple cell types at various stages of skin injury. A literature review was conducted to explore related research on the influence of MSC-EVs on the types of cells involved in wound healing. MSC-EVs show a strong regulatory ability on immune cells involved in the regulation of inflammation, including macrophages, neutrophils, and T cells, and other cells involved in tissue proliferation and remodeling, such as fibroblasts, keratinocytes, and endothelial cells, during wound healing in in vitro and in vivo experiments, which substantially promoted the understanding of wound healing in the field of trauma medicine. MSC-EVs have potential applications in combating poor skin wound healing. Elucidating the mechanism of action of EVs in the wound-healing process would greatly advance the understanding of therapeutic wound healing.
Large-Scale Whole Genome Sequence Analysis of >22,000 Subjects Provides no Evidence of FMR1 Premutation Allele Involvement in Autism Spectrum Disorder
Authors: Chubick Alex , Wang Evan , Au Cora , Grody Wayne W. , Ophoff Roel A.
Published: July 2023

Expansion of a CGG repeat in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome is the cause of Fragile X Syndrome (FXS). The repeat length of unaffected individuals varies between 5–40 repeats, whereas >200 repeats are observed in cases of FXS. The intermediate range between 55–200 repeats is considered the premutation range and is observed in roughly 1:300 females and 1:900 males in the general population. With the availability of large-scale whole genome sequence (WGS) data and the development of computational tools to detect repeat expansions, we systematically examined the role of FMR1 premutation alleles in autism spectrum disorder (ASD) susceptibility, assess the prevalence, and consider the allelic stability between parents and offspring. We analyzed the WGS data of 22,053 subjects, including 32 FXS positive controls, 1359 population controls, and 5467 ASD families. We observed no FMR1 full mutation range repeats among the ASD parent-offspring families but identified 180 family members with premutation range alleles, which represents a higher prevalence compared to the independent WGS control sample and previous reports in the literature. A sex-specific analysis between probands and unaffected siblings did not reveal a significant increase in the burden of premutation alleles in either males or females with ASD. PCR validation, however, suggests an overestimation of the frequency of FMR1 premutation range alleles through computational analysis of WGS data. Overall, we show the utility of large-scale repeat expansion screening in WGS data and conclude that there is no apparent evidence of FMR1 premutation alleles contributing to ASD susceptibility.
Esophageal Dysbiosis in Achalasia and Cancer Development: A Critical Review
Authors: Tustumi Francisco , Arienzo Vitor , Sunye Isabela , Lucas Phellipe , Colonno Bárbara , Quintas Julia , Lisboa Elis , Szor Daniel
Published: July 2023

Background: Microorganisms provide various benefits to their human hosts, including assisting with digestion, synthesizing certain vitamins, developing the gastrointestinal and immune systems, regulating metabolism, and protecting against some pathogens. However, microbial imbalances can cause tissue damage and contribute to inflammatory disorders and cancers. Microbial dysbiosis refers to an imbalance or disruption in the normal composition and function of the microbial communities that inhabit various body parts, including the gut, oral cavity, skin, and reproductive tract. Emerging research suggests that microbial dysbiosis plays a significant role in cancer development and progression. This issue is particularly relevant in achalasia, in which food stasis, changes in endoluminal pH, and poor esophageal clearance might contribute to esophageal microbial dysbiosis. This study aimed to evaluate the association between dysbiosis and esophageal cancer development, focused on esophageal dysmotility disorders. Methods: This study is a critical review, gathering the current evidence for the association between dysbiosis and the development of esophageal cancer. Results: Studies have shown that microbiota play a role in cancer development, although the mechanisms for how they do so are not yet fully understood. One possible explanation is that microbiota alterations can lead to chronic inflammation, promoting cancer cell growth. Additionally, some bacteria produce toxins that can damage DNA and cause genomic instability, and certain bacterial products can promote tumor growth. Conclusion: Despite the close relationship between dysbiosis and cancer development in esophageal dysmotility disorders, further investigations are still needed to elucidate the precise mechanisms by which dysbiosis contributes to cancer development and to identify potential therapeutic interventions targeting the microbiota to prevent or treat cancer.
Art and Storytelling on the Streets: The Council on Interracial Books for Children’s Use of African American Children’s Literature
Authors: Batho Nick
Published: July 2023

From 1970 until 1974, the Council on Interracial Children’s Books (CIBC) ran the Arts and Storytelling in the Streets program throughout New York City. This program involved African American and Puerto Rican artists and storytellers bringing children’s literature directly to children in the streets. This occurred amid a rise in African American children’s literature and educational upheavals in the city as local communities demanded oversight of their schools. Originating in the Ocean Hill-Brownsville district in New York City, the Arts and Storytelling on the Streets program helps to underscore the interrelation between African American children’s literature and educational activism. This article examines how storytelling sessions run by authors and illustrators became extensions of African American children’s literature and educational activism in the city as Black American children’s books became key tools in a fight for a more representative and relevant education. Storytelling teams hoped to use African American children’s literature to help engage children in reading and provide a positive association with literature among local children. The Art and Storytelling program mirrored ideas and themes within African American children’s literature including Black pride, community strength, and resisting white supremacy. The program also became a key extension of the literature as the locations, storytellers, and the audiences all helped to expand upon the impact and many meanings inherent in contemporary African American children’s literature.
Continuous Glucose Monitoring (CGM) in Sports—A Comparison between a CGM Device and Lab-Based Glucose Analyser under Resting and Exercising Conditions in Athletes
Authors: Bauhaus Helen , Erdogan Pinar , Braun Hans , Thevis Mario
Published: July 2023

The objective of this pilot study was to compare glucose concentrations in capillary blood (CB) samples analysed in a laboratory by a validated method and glucose concentrations measured in the interstitial fluid (ISF) by continuous glucose monitoring (CGM) under different physical activity levels in a postprandial state in healthy athletes without diabetes. As a physiological shift occurs between glucose concentration from the CB into the ISF, the applicability of CGM in sports, especially during exercise, as well as the comparability of CB and ISF data necessitate an in-depth assessment. Ten subjects (26 ± 4 years, 67 ± 11 kg bodyweight (BW), 11 ± 3 h) were included in the study. Within 14 days, they underwent six tests consisting of (a) two tests resting fasted (HC_Rest/Fast and LC_Rest/Fast), (b) two tests resting with intake of 1 g glucose/kg BW (HC_Rest/Glc and LC_Rest/Glc), (c) running for 60 min at moderate (ModExerc/Glc), and (d) high intensity after intake of 1 g glucose/kg BW (IntExerc/Glc). Data were collected in the morning, following a standardised dinner before test day. Sensor-based glucose concentrations were compared to those determined from capillary blood samples collected at the time of sensor-based analyses and subjected to laboratory glucose measurements. Pearson’s r correlation coefficient was highest for Rest/Glc (0.92, p < 0.001) compared to Rest/Fast (0.45, p < 0.001), ModExerc/Glc (0.60, p < 0.001) and IntExerc/Glc (0.70, p < 0.001). Mean absolute relative deviation (MARD) and standard deviation (SD) was smallest for resting fasted and similar between all other conditions (Rest/Fast: 8 ± 6%, Rest/Glc: 17 ± 12%, ModExerc/Glc: 22 ± 24%, IntExerc/Glc: 18 ± 17%). However, Bland–Altman plot analysis showed a higher range between lower and upper limits of agreement (95% confidence interval) of paired data under exercising compared to resting conditions. Under resting fasted conditions, both methods produce similar outcomes. Under resting postprandial and exercising conditions, respectively, there are differences between both methods. Based on the results of this study, the application of CGM in healthy athletes is not recommended without concomitant nutritional or medical advice.
Biomarkers for Immune Checkpoint Inhibitor Response in NSCLC: Current Developments and Applicability
Authors: Tostes Katiane , Siqueira Aléxia Polo , Reis Rui Manuel , Leal Leticia Ferro , Arantes Lidia Maria Rebolho Batista
Published: July 2023

Lung cancer has the highest mortality rate among all cancer types, resulting in over 1.8 million deaths annually. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC). ICIs, predominantly monoclonal antibodies, modulate co-stimulatory and co-inhibitory signals crucial for maintaining immune tolerance. Despite significant therapeutic advancements in NSCLC, patients still face challenges such as disease progression, recurrence, and high mortality rates. Therefore, there is a need for predictive biomarkers that can guide lung cancer treatment strategies. Currently, programmed death-ligand 1 (PD-L1) expression is the only established biomarker for predicting ICI response. However, its accuracy and robustness are not consistently reliable. This review provides an overview of potential biomarkers currently under development or in the validation stage that hold promise in improving the classification of responders and non-responders to ICI therapy in the near future.
Genome-Wide Identification of the NF-Y Gene Family and Their Involvement in Bolting and Flowering in Flowering Chinese Cabbage
Authors: Jiang Zhehao , Wang Yuting , Li Wenxiang , Wang Yudan , Liu Xiaojuan , Ou Xi , Su Wei , Song Shiwei , Chen Riyuan
Published: July 2023

Flowering Chinese cabbage (Brassica campestris L. ssp. Chinensis var. utilis Tsen et Lee) is a widely consumed vegetable in southern China with significant economic value. Developing product organs in the flowering Chinese cabbage involves two key processes: bolting and flowering. Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor known for its crucial role in various plant developmental processes. However, there is limited information available on the involvement of this gene family during flowering during Chinese cabbage development. In this study, 49 BcNF-Y genes were identified and characterized along with their physicochemical properties, gene structure, chromosomal location, collinearity, and expression patterns. We also conducted subcellular localization, yeast two-hybrid, and transcriptional activity assays on selected BcNF-Y genes. The findings of this study revealed enhanced expression levels of specific BcNF-Y genes during the stalk development and flowering stages in flowering Chinese cabbage. Notably, BcNF-YA8, BcNF-YB14, BcNF-YB20, and BcNF-YC5 interacted with BcRGA1, a negative regulator of GA signaling, indicating their potential involvement in GA-mediated stalk development. This study provides valuable insights into the role of BcNF-Y genes in flowering Chinese cabbage development and suggests that they are potential candidates for further investigating the key regulators of cabbage bolting and flowering.
Conservation of Markers and Stemness in Adipose Stem and Progenitor Cells between Cattle and Other Species
Authors: Ishida Yuki , Mabuchi Yo , Naraoka Yuna , Hisamatsu Daisuke , Akazawa Chihiro
Published: July 2023

Adipose stem and progenitor cells (ASPCs) have been isolated from humans and animals for use in regenerative medicine and therapy. However, knowledge of ASPCs in other species is limited. Particularly, ASPCs in livestock are expected to enhance the fat content and meat composition. In this study, we isolated bovine ASPCs using cell surface markers. Specifically, we focused on ASPC markers in humans and experimental animals, namely CD26, CD146, and CD54. Stromal vascular fraction cells from bovine fat were separated using flow cytometry before primary culture. We evaluated the self-renewal and adipogenic potential of each fraction. We identified four cell populations: CD26−CD146+CD54+, CD26−CD146+CD54−, CD26−CD146−, and CD26+CD146−. Among them, the CD26−CD146+ fraction, particularly CD54+, demonstrated the properties of preadipocytes (PreAs), characterized by slow proliferation and a high adipogenic capacity. In conclusion, we could collect and characterize possible PreAs as CD26−CD146+CD54+ or CD26−CD146+CD54−, which are expected for in vitro bovine adipogenic assays in the future.
Metabolic Oscillations and Glycolytic Phenotypes of Cancer Cells
Authors: Amemiya Takashi , Shibata Kenichi , Yamaguchi Tomohiko
Published: July 2023

Cancer cells show several metabolic phenotypes depending on the cancer types and the microenvironments in tumor tissues. The glycolytic phenotype is one of the hallmarks of cancer cells and is considered to be one of the crucial features of malignant cancers. Here, we show glycolytic oscillations in the concentrations of metabolites in the glycolytic pathway in two types of cancer cells, HeLa cervical cancer cells and DU145 prostate cancer cells, and in two types of cellular morphologies, spheroids and monolayers. Autofluorescence from nicotinamide adenine dinucleotide (NADH) in cells was used for monitoring the glycolytic oscillations at the single-cell level. The frequencies of NADH oscillations were different among the cellular types and morphologies, indicating that more glycolytic cancer cells tended to exhibit oscillations with higher frequencies than less glycolytic cells. A mathematical model for glycolytic oscillations in cancer cells reproduced the experimental results quantitatively, confirming that the higher frequencies of oscillations were due to the higher activities of glycolytic enzymes. Thus, glycolytic oscillations are expected as a medical indicator to evaluate the malignancy of cancer cells with glycolytic phenotypes.
Resistin-like Molecule α and Pulmonary Vascular Remodeling: A Multi-Strain Murine Model of Antigen and Urban Ambient Particulate Matter Co-Exposure
Authors: Durmus Nedim , Chen Wen-Chi , Park Sung-Hyun , Marsh Leigh M. , Kwon Sophia , Nolan Anna , Grunig Gabriele
Published: July 2023

Pulmonary hypertension (PH) has a high mortality and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type-2- and type-17 responses in C57BL/6 mice. Here, we focused on type-2-response-related cytokines, specifically resistin-like molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild-type or RELMα−/− mice. Vascular remodeling was assessed with histology; right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were much more prominent in the C57BL/6 strain. Compared to wild-type mice, RELMα−/− had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV IL-33-receptor were significantly increased in BALB/c wild-type mice, but not in BALB/c-RELMα−/− or in C57BL/6-wild-type or C57BL/6-RELMα−/− mice in response to antigen/PM2.5. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα−/− mice were not different from their respective wild-type controls. The RELMα−/− animals demonstrated significantly decreased expression of RELMβ and RELMγ, which makes these mice comparable to a situation where human RELMβ levels would be significantly modified, as only humans have this single RELM molecule. In BALB/c mice, RELMα was a key contributor to pulmonary vascular remodeling, increase in RV weight and RV cytokine responses induced by exposure to antigen/PM2.5, highlighting the significance of the genetic background for the biological role of RELMα.
Compromised Mitotic Fidelity in Human Pluripotent Stem Cells
Authors: Milagre Inês , Pereira Carolina , Oliveira Raquel A.
Published: July 2023

Human pluripotent stem cells (PSCs), which include both embryonic and induced pluripotent stem cells, are widely used in fundamental and applied biomedical research. They have been instrumental for better understanding development and cell differentiation processes, disease origin and progression and can aid in the discovery of new drugs. PSCs also hold great potential in regenerative medicine to treat or diminish the effects of certain debilitating diseases, such as degenerative disorders. However, some concerns have recently been raised over their safety for use in regenerative medicine. One of the major concerns is the fact that PSCs are prone to errors in passing the correct number of chromosomes to daughter cells, resulting in aneuploid cells. Aneuploidy, characterised by an imbalance in chromosome number, elicits the upregulation of different stress pathways that are deleterious to cell homeostasis, impair proper embryo development and potentiate cancer development. In this review, we will summarize known molecular mechanisms recently revealed to impair mitotic fidelity in human PSCs and the consequences of the decreased mitotic fidelity of these cells. We will finish with speculative views on how the physiological characteristics of PSCs can affect the mitotic machinery and how their suboptimal mitotic fidelity may be circumvented.
Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation
Authors: Fakhimahmadi Aila , Hasanaj Ilir , Hofstetter Gerlinde , Pogner Clara , Gorfer Markus , Wiederstein Markus , Szepannek Nathalie , Bianchini Rodolfo , Dvorak Zdenek , Jensen Sebastian A. , Berger Markus , Jensen-Jarolim Erika , Hufnagl Karin , Roth-Walter Franziska
Published: July 2023

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron–quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo– or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo– and holo–Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation.
Amino Acid Metabolism and Disease
Authors: Pajares María Ángeles
Published: July 2023

The origin of life is still a matter of debate, and several hypotheses have been proposed to explain how the building blocks leading to the minimal cell were formed [...]
Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment
Authors: Nishio Hisahide , Niba Emma Tabe Eko , Saito Toshio , Okamoto Kentaro , Takeshima Yasuhiro , Awano Hiroyuki
Published: July 2023

Spinal muscular atrophy (SMA) is a lower motor neuron disease with autosomal recessive inheritance. The first cases of SMA were reported by Werdnig in 1891. Although the phenotypic variation of SMA led to controversy regarding the clinical entity of the disease, the genetic homogeneity of SMA was proved in 1990. Five years later, in 1995, the gene responsible for SMA, SMN1, was identified. Genetic testing of SMN1 has enabled precise epidemiological studies, revealing that SMA occurs in 1 of 10,000 to 20,000 live births and that more than 95% of affected patients are homozygous for SMN1 deletion. In 2016, nusinersen was the first drug approved for treatment of SMA in the United States. Two other drugs were subsequently approved: onasemnogene abeparvovec and risdiplam. Clinical trials with these drugs targeting patients with pre-symptomatic SMA (those who were diagnosed by genetic testing but showed no symptoms) revealed that such patients could achieve the milestones of independent sitting and/or walking. Following the great success of these trials, population-based newborn screening programs for SMA (more precisely, SMN1-deleted SMA) have been increasingly implemented worldwide. Early detection by newborn screening and early treatment with new drugs are expected to soon become the standards in the field of SMA.
An IIoT-Device for Acquisition and Analysis of High-Frequency Data Processed by Artificial Intelligence
Authors: Kneifel Jens , Roj Robin , Woyand Hans-Bernhard , Theiß Ralf , Dültgen Peter
Published: July 2023

This publication presents the development of an Industrial-Internet-of-Things device. The device is capable of completing several tasks, such as the acquisition of high-frequency measurement data and evaluating data via machine learning methods in an artificial intelligence application. The installed measurement technology generates data which is comparable to data generated by costly laboratory equipment, meaning that it can be used as a low-budget and open-source alternative. A workflow method has been designed that promotes experimental work and simplifies the effort required to implement artificial intelligence solutions. At the end of this paper, the results of the experiment, which aimed to collect measurement data, extract suitable features, and train artificial intelligence models, are presented. Techniques from vibration analysis were used for feature extraction, and concepts for the extrapolation and enhancement of data sets were investigated. The test results have proven that the development is comparable with high-end laboratory equipment. The created application has demonstrated sufficient accuracy in predictions, and the designed process can be used for arbitrary, artificial intelligence-based rapid prototyping.
Associations between Vertebral Localized Contrast Changes and Adjacent Annular Fissures in Patients with Low Back Pain: A Radiomics Approach
Authors: Waldenberg Christian , Brisby Helena , Hebelka Hanna , Lagerstrand Kerstin Magdalena
Published: July 2023

Low back pain (LBP) is multifactorial and associated with various spinal tissue changes, including intervertebral disc fissures, vertebral pathology, and damaged endplates. However, current radiological markers lack specificity and individualized diagnostic capability, and the interactions between the various markers are not fully clear. Radiomics, a data-driven analysis of radiological images, offers a promising approach to improve evaluation and deepen the understanding of spinal changes related to LBP. This study investigated possible associations between vertebral changes and annular fissures using radiomics. A dataset of 61 LBP patients who underwent conventional magnetic resonance imaging followed by discography was analyzed. Radiomics features were extracted from segmented vertebrae and carefully reduced to identify the most relevant features associated with annular fissures. The results revealed three important texture features that display concentrated high-intensity gray levels, extensive regions with elevated gray levels, and localized areas with reduced gray levels within the vertebrae. These features highlight patterns within vertebrae that conventional classification systems cannot reflect on distinguishing between vertebrae adjacent to an intervertebral disc with or without an annular fissure. As such, the present study reveals associations that contribute to the understanding of pathophysiology and may provide improved diagnostics of LBP.
Assessment by Women on Selected Aspects of Quality of Life and on Disease Acceptance after Undergoing Urogynecological Procedures for Urinary Incontinence
Authors: Baczewska Bożena , Wiśniewska Katarzyna , Muraczyńska Bożena , Pasek Małgorzata , Słuszniak Jolanta , Gębicka Katarzyna , Guzak Beata
Published: July 2023

Urinary incontinence is a common social and health problem that affects both men and women. Women, however, are twice as likely as men to experience unintentional and involuntary bladder emptying due to their anatomical structure and biological functions. Urinary incontinence is associated with great discomfort, a sense of shame, and a significant reduction in self-esteem, often resulting in the limiting of, or withdrawing from, professional, social, and community life. The aim of this study was to evaluate selected aspects of the quality of life and disease acceptance by women who had undergone urogynecological procedures for urinary incontinence. The study encompassed 77 women. The diagnostic tools used in the study were the Polish versions of the King’s Health Questionnaire (KHQ), the Acceptance of Illness Scale (AIS), and the authors’ own survey questionnaire. From the undertaken research, we found that women with urinary incontinence who underwent urogynecological procedures rated their overall health well. What worsened the most regarding the quality of life of women post-procedure for urinary incontinence was the impact of bladder problems on their lives and the discomfort they felt due to bladder problems. The relationship between the time elapsed since the procedure and the quality of life of the respondents with regard to the emotions they experienced was also found to be significant. The longer the time since the procedure, the lower the intensity of negative emotions, and thus the higher the quality of life. Despite the varied opinions of the respondents about the impact of bladder dysfunction on various areas of their lives, acceptance of the disease, as measured by the AIS scale, appeared to be high.
The Effectiveness of a Multimodal Brain Empowerment Program in Mild Cognitive Impairment: A Single-Blind, Quasi-Randomized Experimental Study
Authors: Oh Wonjun , Park Haeun , Hallett Mark , You Joshua (Sung) H.
Published: July 2023

The present study aimed to determine a multimodal brain empowerment (MBE) program to mitigate the modifiable risk factors in mild cognitive impairment (MCI), and its therapeutic effects are unknown. MBE encompassing (1) tDCS, light therapy, computerized cognitive therapy (TLC) and (2) robot-assisted gait training, music therapy, and core exercise (REM) interventions were randomly assigned to 20 healthy young adults and 20 older adults with MCI. The electroencephalography (EEG) power spectrum and topographic event-related synchronization (ERS) analysis were used to assess intervention-related changes in neural activity during the MBE program. Outcome: The EEG results demonstrated that both multimodal TLC and REM decreased delta waves and increased theta, alpha, and beta waves (p < 0.001). ERS showed increased neural activation in the frontal, temporal, and parietal lobes during TLC and REM. Such enhanced neural activity in the region of interest supports potential clinical benefits in empowering cognitive function in both young adults and older adults with MCI.
Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases
Authors: Soko Nyarai Desiree , Muyambo Sarudzai , Dandara Michelle T. L. , Kampira Elizabeth , Blom Dirk , Jones Erika S. W. , Rayner Brian , Shamley Delva , Sinxadi Phumla , Dandara Collet
Published: July 2023

Pharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug–gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.