bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of plantation age on plant and soil C:N:P stoichiometry in Kentucky bluegrass pastures
Authors: Wei Xiaoxing , He Keyan , Wang Qian , Liu Wenhui , Pang Xiaopan , Guo Zhenggang
Published: March 2024

Plant and soil C:N:P stoichiometry reflects the element content and energy flow, which are important for biogeochemical cycling in ecosystems. Although plantation age has been verified to affect leaf C:N:P stoichiometry in alfalfa plants, its effect on plant and soil C:N:P stoichiometry in grass remains poorly documented. A 10-year field experiment of Kentucky bluegrass (Poa pratensis) was used to test how plantation age affect plant and soil C:N:P stoichiometry in a perennial rhizomatous grass pasture. This study demonstrated that leaf C:N, C:P, and N:P ratios exhibited a rapid increasing trend from 2 to 6 years of age, whereas leaf C:N showed a slight decreasing trend, and leaf C:P and N:P maintained stability from 6 to 9 years of age. Stem C:N and N:P were not different among plantation ages, while stem C:P increased from 2 to 4 years of plantation age and then maintained stability from 4 to 9 years of plantation age. Root N:P showed an increasing trend from 2 to 6 years of plantation age and relative stability from 6 to 9 years of plantation age, whereas root C:N and C:P showed decreasing trends from 2 to 9 years of plantation age. Although soil C:P did not differ among nine plantation ages, soil C:N and N:P remained relatively stable from 2 to 6 years of plantation age. However, soil C:N showed a decreasing trend, while soil N:P showed an increasing trend after 6 years of plantation age. The results from an ecological stoichiometric homeostasis analysis further showed that N in the leaf, stem, and root and P in the stem had strict homeostasis, whereas P in the leaf and root showed plastic and weakly homeostatic status, respectively. These results present a pattern concerning the plantation age in relation to plant and soil C:N:P stoichiometry in a perennial grass and provide useful information for N and P management in Kentucky bluegrass pastures.
Copy number variants selected during pig domestication inferred from whole genome resequencing
Authors: Zhang Wei , Xu Chengliang , Zhou Mei , Liu Linqing , Ni Zelan , Su Shiguang , Wang Chonglong
Published: March 2024

Over extended periods of natural and artificial selection, China has developed numerous exceptional pig breeds. Deciphering the germplasm characteristics of these breeds is crucial for their preservation and utilization. While many studies have employed single nucleotide polymorphism (SNP) analysis to investigate the local pig germplasm characteristics, copy number variation (CNV), another significant type of genetic variation, has been less explored in understanding pig resources. In this study, we examined the CNVs of 18 Wanbei pigs (WBP) using whole genome resequencing data with an average depth of 12.61. We identified a total of 8,783 CNVs (~30.07 Mb, 1.20% of the pig genome) in WBP, including 8,427 deletions and 356 duplications. Utilizing fixation index (Fst), we determined that 164 CNVs were within the top 1% of the Fst value and defined as under selection. Functional enrichment analyses of the genes associated with these selected CNVs revealed genes linked to reproduction (SPATA6, CFAP43, CFTR, BPTF), growth and development (NR6A1, SMYD3, VIPR2), and immunity (PARD3, FYB2). This study enhances our understanding of the genomic characteristics of the Wanbei pig and offers a theoretical foundation for the future breeding of this breed.
A Novel Approach for Predicting Anthropogenic CO2 Emissions Using Machine Learning Based on Clustering of the CO2 Concentration
Authors: Ji Zhanghui , Song Hao , Lei Liping , Sheng Mengya , Guo Kaiyuan , Zhang Shaoqing
Published: March 2024

The monitoring of anthropogenic CO2 emissions, which increase the atmospheric CO2 concentration, plays the most important role in the management of emission reduction and control. With the massive increase in satellite-based observation data related to carbon emissions, a data-driven machine learning method has great prospects for predicting anthropogenic CO2 emissions. Training samples, which are used to model predictions of anthropogenic CO2 emissions through machine learning algorithms, play a key role in obtaining accurate predictions for the spatial heterogeneity of anthropogenic CO2 emissions. We propose an approach for predicting anthropogenic CO2 emissions using the training datasets derived from the clustering of the atmospheric CO2 concentration and the segmentation of emissions to resolve the issue of the spatial heterogeneity of anthropogenic CO2 emissions in machine learning modeling. We assessed machine learning algorithms based on decision trees and gradient boosting (GBDT), including LightGBM, XGBoost, and CatBoost. We used multiple parameters related to anthropogenic CO2-emitting activities as predictor variables and emission inventory data from 2019 to 2021, and we compared and verified the accuracy and effectiveness of different prediction models based on the different sampling methods of training datasets combined with machine learning algorithms. As a result, the anthropogenic CO2 emissions predicted by CatBoost modeling from the training dataset derived from the clustering analysis and segmentation method demonstrated optimal prediction accuracy and performance for revealing anthropogenic CO2 emissions. Based on a machine learning algorithm using observation data, this approach for predicting anthropogenic CO2 emissions could help us quickly obtain up-to-date information on anthropogenic CO2 emissions as one of the emission monitoring tools.
Cortical Sensorimotor Integration as a Neural Origin of Impaired Grip Force Direction Control following Stroke
Authors: Schranz Christian , Seo Na Jin
Published: March 2024

Background: Stroke is a major cause of disability worldwide. Upper limb impairment is prevalent after stroke. One of the post-stroke manifestations is impaired grip force directional control contributing to diminished abilities to grip and manipulate objects necessary for activities of daily living. The objective of this study was to investigate the neural origin of the impaired grip force direction control following stroke. Due to the importance of online adjustment of motor output based on sensory feedback, it was hypothesized that grip force direction control would be associated with cortical sensorimotor integration in stroke survivors. Methods: Ten chronic stroke survivors participated in this study. Cortical sensorimotor integration was quantified by short latency afferent inhibition (SAI), which represents the responsiveness of the primary motor cortex to somatosensory input. Grip force direction control was assessed during paretic grip. Results: Grip force direction control was significantly associated with SAI. This relationship was independent of sensory impairment level. Conclusions: Cortical sensorimotor integration may play a significant role in the grip force direction control important for gripping and manipulating objects with the affected hand following stroke. This knowledge may be used to inform personalized rehabilitation treatment. For example, for patients with impaired grip force direction control, behavioral therapy focusing on feedback motor control, augmented by use of brain stimulation to reinforce cortical sensorimotor integration such as paired associative stimulation, may be applied.
A Fast and Robust Safety Helmet Network Based on a Mutilscale Swin Transformer
Authors: Xiang Changcheng , Yin Duofen , Song Fei , Yu Zaixue , Jian Xu , Gong Huaming
Published: March 2024

Visual inspection of the workplace and timely reminders of unsafe behaviors (e.g, not wearing a helmet) are particularly significant for avoiding injuries to workers on the construction site. Video surveillance systems generate large amounts of non-structure image data on site for this purpose; however, they require real-time recognition automation solutions based on computer vision. Although various deep-learning-based models have recently provided new ideas for identifying helmets in traffic monitoring, few solutions suitable for industry applications have been discussed due to the complex scenarios of construction sites. In this paper, a fast and robust network based on a mutilscale Swin Transformer is proposed for safety helmet detection (FRSHNet) at construction sites, which contains the following contributions. Firstly, MAE-NAS with the variant of MobileNetV3’s MobBlock as a basic block is applied to implement feature extraction. Simultaneously, a multiscale Swin Transformer module is utilized to obtain the spatial and contexture relationships in the multiscale features. Subsequently, in order to meet the scheme requirements of real-time helmet detection, efficient RepGFPN are adopted to integrate refined multiscale features to form a pyramid structure. Extensive experiments were conducted on the publicly available Pictor-v3 and SHWD datasets. The experimental results show that FRSHNet consistently provided a favorable performance, outperforming the existing state-of-the-art models.
Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts
Authors: Asumda Faizal Z. , Campbell Nellie A. , Hassan Mohamed A. , Fathi Reza , Vasquez Rico Daniella F. , Kiem Melanie , Vang Ethan V. , Kim Yo Han , Luo Xin , O’Brien Daniel R. , Buhrow Sarah A. , Reid Joel M. , Moore Michael J. , Ben-Yair Vered Katz , Levitt Mark L. , Leiting Jennifer L. , Abdelrahman Amro M. , Zhu Xinli , Lucien Fabrice , Truty Mark J. , Roberts Lewis R.
Published: March 2024

Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude mice. PAX165, a patient-derived xenograft (PDX) from a surgically resected CCA, expresses substantial levels of SPHK2, PRSS1, PRSS2, and PRSS3. Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group.
Chimeric Antigen Receptor-Modified T Cell Therapy in Metastatic Castrate-Resistant Prostate Cancer: Promise and Potential
Authors: Tharian Leah R. , Verma Shiv , Gupta Sanjay
Published: March 2024

Prostate cancer, the most common cancer among males, has a mortality rate of approximately 29,000 deaths each year in the United States alone [...]
Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention
Authors: Muranaka Hayato , Akinsola Rasaq , Billet Sandrine , Pandol Stephen J. , Hendifar Andrew E. , Bhowmick Neil A. , Gong Jun
Published: March 2024

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.
Sonographic Measurements of Rectus Femoris Muscle Thickness Strongly Predict Neutropenia in Cancer Patients Receiving Chemotherapy
Authors: Güner Gürkan , Özçakar Levent , Baytar Yusuf , Onur Mehmet Ruhi , Demir Metin , Aktaş Burak Yasin , Aktepe Oktay Halit , Güven Deniz Can , Taban Hakan , Yıldırım Hasan Çağrı , Akın Serkan , Aksoy Sercan , Kara Murat , Dizdar Ömer
Published: March 2024

The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)—assessed by computed tomography (CT) and ultrasound (US)—and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3–4 neutropenia by 9.210 times (95% CI = 2.401–35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.
Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases
Authors: Bartman Sydney , Coppotelli Giuseppe , Ross Jaime M.
Published: March 2024

Mitochondria are thought to have become incorporated within the eukaryotic cell approximately 2 billion years ago and play a role in a variety of cellular processes, such as energy production, calcium buffering and homeostasis, steroid synthesis, cell growth, and apoptosis, as well as inflammation and ROS production. Considering that mitochondria are involved in a multitude of cellular processes, mitochondrial dysfunction has been shown to play a role within several age-related diseases, including cancers, diabetes (type 2), and neurodegenerative diseases, although the underlying mechanisms are not entirely understood. The significant increase in lifespan and increased incidence of age-related diseases over recent decades has confirmed the necessity to understand the mechanisms by which mitochondrial dysfunction impacts the process of aging and age-related diseases. In this review, we will offer a brief overview of mitochondria, along with structure and function of this important organelle. We will then discuss the cause and consequence of mitochondrial dysfunction in the aging process, with a particular focus on its role in inflammation, cognitive decline, and neurodegenerative diseases, such as Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease. We will offer insight into therapies and interventions currently used to preserve or restore mitochondrial functioning during aging and neurodegeneration.
A Survival Analysis of Patients with Recurrent Epithelial Ovarian Cancer Based on Relapse Type: A Multi-Institutional Retrospective Study in Armenia
Authors: Harutyunyan Lilit , Manvelyan Evelina , Karapetyan Nune , Bardakhchyan Samvel , Jilavyan Aram , Tamamyan Gevorg , Avagyan Armen , Safaryan Liana , Zohrabyan Davit , Movsisyan Narine , Avinyan Anna , Galoyan Arevik , Sargsyan Mariam , Harutyunyan Martin , Nersoyan Hasmik , Stepanyan Arevik , Galstyan Armenuhi , Danielyan Samvel , Muradyan Armen , Jilavyan Gagik
Published: March 2024

Background: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. Methods: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. Results: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.
Hybrid LSTM-Based Fractional-Order Neural Network for Jeju Island’s Wind Farm Power Forecasting
Authors: Ramadevi Bhukya , Kasi Venkata Ramana , Bingi Kishore
Published: March 2024

Efficient integration of wind energy requires accurate wind power forecasting. This prediction is critical in optimising grid operation, energy trading, and effectively harnessing renewable resources. However, the wind’s complex and variable nature poses considerable challenges to achieving accurate forecasts. In this context, the accuracy of wind parameter forecasts, including wind speed and direction, is essential to enhancing the precision of wind power predictions. The presence of missing data in these parameters further complicates the forecasting process. These missing values could result from sensor malfunctions, communication issues, or other technical constraints. Addressing this issue is essential to ensuring the reliability of wind power predictions and the stability of the power grid. This paper proposes a long short-term memory (LSTM) model to forecast missing wind speed and direction data to tackle these issues. A fractional-order neural network (FONN) with a fractional arctan activation function is also developed to enhance generated wind power prediction. The predictive efficacy of the FONN model is demonstrated through two comprehensive case studies. In the first case, wind direction and forecast wind speed data are used, while in the second case, wind speed and forecast wind direction data are used for predicting power. The proposed hybrid neural network model improves wind power forecasting accuracy and addresses data gaps. The model’s performance is measured using mean errors and R2 values.
Network Screening on Low-Volume Roads Using Risk Factors
Authors: Huda Kazi Tahsin , Al-Kaisy Ahmed
Published: March 2024

This paper proposes a new method for network screening on rural low-volume roads. These roads are important as they provide critical access to agricultural land and tourist attractions. Most low-volume roads belong to the lowest functional class (local rural roads) and thus are built to lower design standards. Conventional hot spot network screening techniques may not be appropriate for low-volume roads due to the sporadic nature of crashes occurring on these roads. Conversely, sophisticated network screening approaches require extensive roadway and traffic data that are often unavailable to local agencies due to a lack of resources, and/or a lack of technical expertise. This research attempts to address these obstacles to low-volume road network screening which aims to identify candidate sites for safety improvements. The research used an extensive low-volume road sample from the state of Oregon and Empirical Bayes expected number of crashes in developing the proposed models for network screening. The proposed models do not require exact measurements of roadway geometric features as all geometric variables were classified into categories that are easy to compile by local agencies. Further, the method could be used with and without traffic data, without compromising the effectiveness of the network screening process.
Genomic and Expression Analysis of Cassava (Manihot esculenta Crantz) Chalcone Synthase Genes in Defense against Tetranychus cinnabarinus Infestation
Authors: Yang Yanni , Liu Ming , Huang Zenghui
Published: March 2024

Cassava is susceptible to mites, especially Tetranychus cinnabarinus. Secondary metabolism products such as flavonoids play an important role as antimicrobial metabolites protecting plants against biotic stressors including fungal, pathogen, bacterial, and pest defense. The chalcone synthase (CHS) is the initial step of the phenylpropanoid pathway for producing flavonoids and is the gatekeeper of the pathway. Until recently, the CHS genes family has not been systematically studied in cassava. Thirty-nine CHS genes were identified from the cassava genome database. Based on phylogenetic and sequence composition analysis, these CHSs were divided into 3 subfamilies. Within the same subfamily, the gene structure and motif compositions of these CHS genes were found to be quite conserved. Duplication events, particularly segmental duplication of the cassava CHS genes, were identified as one of the main driving force of its expansion. Various cis-elements contained in the promoter might regulate the gene expression patterns of MeCHS. Protein-protein interaction (PPI) network analysis showed that MeCHS1 and MeCHS10 protein are more closely related to other family members. The expression of MeCHS genes in young leaves was higher than that in other tissues, and their expression varies even within the same tissue. Coincidentally, these CHS genes of most LAP subclasses were highly expressed in young leaves. The verified MeCHS genes showed consistent with the real-time reverse transcription quantitative PCR (RT-qPCR) and proteomic expression in protected and affected leaves respectively, indicating that these MeCHS genes play crucial roles in the response to T. cinnabarinus. This study is the first to comprehensively expatiate the information on MeCHS family members. These data will further enhance our understanding both the molecular mechanisms and the effects of CHS genes. In addition, the results will help to further clarify the effects on T. cinnabarinus and provide a theoretical basis for the potential functions of the specific CHS gene in resistance to mites and other biotic stress.
Role of Post-Transcriptional Regulation in Learning and Memory in Mammals
Authors: Di Liegro Carlo Maria , Schiera Gabriella , Schirò Giuseppe , Di Liegro Italia
Published: March 2024

After many decades, during which most molecular studies on the regulation of gene expression focused on transcriptional events, it was realized that post-transcriptional control was equally important in order to determine where and when specific proteins were to be synthesized. Translational regulation is of the most importance in the brain, where all the steps of mRNA maturation, transport to different regions of the cells and actual expression, in response to specific signals, constitute the molecular basis for neuronal plasticity and, as a consequence, for structural stabilization/modification of synapses; notably, these latter events are fundamental for the highest brain functions, such as learning and memory, and are characterized by long-term potentiation (LTP) of specific synapses. Here, we will discuss the molecular bases of these fundamental events by considering both the role of RNA-binding proteins (RBPs) and the effects of non-coding RNAs involved in controlling splicing, editing, stability and translation of mRNAs. Importantly, it has also been found that dysregulation of mRNA metabolism/localization is involved in many pathological conditions, arising either during brain development or in the adult nervous system.
Female Sexual Violence: A 12-Year Experience at a Single University Hospital in North-East Italy
Authors: Xodo Serena , Tius Veronica , Baccarini Giovanni , Driul Lorenza
Published: March 2024

This retrospective study analyzed a case series of female sexual violence (SV) victims who were admitted to the emergency department of the University Hospital in Udine between January 2012 and April 2023. A total of 155 cases were divided into two groups according to their age: 115 adult victims and 40 minors. Compared with minors, adults had risk factors such as psychiatric disorders and past experience of SV, and reported bodily injuries and extragenital lesions more frequently. Moreover, a positive screening for sexually transmitted diseases and its association with genital injuries turned out to be significantly more present among adult victims than minors. In contrast, victims younger than 18 years tended to delay seeking medical help and more often did not report genital penetration. To conclude, a deeper knowledge of the different characteristics of sexual abuse among female adults and minors may help us to understand what the focus of prevention programs and public awareness campaigns should be.
Emerging Role of GCN1 in Disease and Homeostasis
Authors: Tatara Yota , Kasai Shuya , Kokubu Daichi , Tsujita Tadayuki , Mimura Junsei , Itoh Ken
Published: March 2024

GCN1 is recognized as a factor that is essential for the activation of GCN2, which is a sensor of amino acid starvation. This function is evolutionarily conserved from yeast to higher eukaryotes. However, recent studies have revealed non-canonical functions of GCN1 that are independent of GCN2, such as its participation in cell proliferation, apoptosis, and the immune response, beyond the borders of species. Although it is known that GCN1 and GCN2 interact with ribosomes to accomplish amino acid starvation sensing, recent studies have reported that GCN1 binds to disomes (i.e., ribosomes that collide each other), thereby regulating both the co-translational quality control and stress response. We propose that GCN1 regulates ribosome-mediated signaling by dynamically changing its partners among RWD domain-possessing proteins via unknown mechanisms. We recently demonstrated that GCN1 is essential for cell proliferation and whole-body energy regulation in mice. However, the manner in which ribosome-initiated signaling via GCN1 is related to various physiological functions warrants clarification. GCN1-mediated mechanisms and its interaction with other quality control and stress response signals should be important for proteostasis during aging and neurodegenerative diseases, and may be targeted for drug development.
Exploring Individual Variability in Drug-Induced Liver Injury (DILI) Responses through Metabolomic Analysis
Authors: Moreno-Torres Marta , Quintás Guillermo , Martínez-Sena Teresa , Jover Ramiro , Castell José V.
Published: March 2024

Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization. Through the identification of various metabolites in the plasma (including free and conjugated bile acids and glycerophospholipids), and the integration of this information into predictive models, we were able to evaluate the extent of the hepatocellular or cholestatic phenotype and to assign a numeric value with the contribution of each specific DILI sub-phenotype into the patient’s general condition. Additionally, our results showed that metabolomic analysis enabled the monitoring of DILI variability responses to the same drug, the transitions between sub-phenotypes during disease progression, and identified a spectrum of residual DILI metabolic features, which can be overlooked using standard clinical diagnosis during patient follow-up.
Utility of 1.5 Tesla MRI Scanner in the Management of Small Sample Sizes Driven from 3D Breast Cell Culture
Authors: Guz Wiesław , Podgórski Rafał , Aebisher David , Truszkiewicz Adrian , Machorowska-Pieniążek Agnieszka , Cieślar Grzegorz , Kawczyk-Krupka Aleksandra , Bartusik-Aebisher Dorota
Published: March 2024

The aim of this work was to use and optimize a 1.5 Tesla magnetic resonance imaging (MRI) system for three-dimensional (3D) images of small samples obtained from breast cell cultures in vitro. The basis of this study was to design MRI equipment to enable imaging of MCF-7 breast cancer cell cultures (about 1 million cells) in 1.5 and 2 mL glass tubes and/or bioreactors with an external diameter of less than 20 mm. Additionally, the development of software to calculate longitudinal and transverse relaxation times is described. Imaging tests were performed using a clinical MRI scanner OPTIMA 360 manufactured by GEMS. Due to the size of the tested objects, it was necessary to design additional receiving circuits allowing for the study of MCF-7 cell cultures placed in glass bioreactors. The examined sample’s volume did not exceed 2.0 mL nor did the number of cells exceed 1 million. This work also included a modification of the sequence to allow for the analysis of T1 and T2 relaxation times. The analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MR images saved in the DICOM3.0 standard which ensures that the data analyzed are reliable and unchangeable in an unintentional manner that could affect the measurement results. The possibility of using 1.5 T MRI systems for cell culture research providing quantitative information from in vitro studies was realized. The scanning resolution for FOV = 5 cm and the matrix was achieved at a level of resolution of less than 0.1 mm/pixel. Receiving elements were built allowing for the acquisition of data for MRI image reconstruction confirmed by images of a phantom with a known structure and geometry. Magnetic resonance sequences were modified for the saturation recovery (SR) method, the purpose of which was to determine relaxation times. An application in MATLAB was developed that allows for the analysis of T1 and T2 relaxation times. The relaxation times of cell cultures were determined over a 6-week period. In the first week, the T1 time value was 1100 ± 40 ms, which decreased to 673 ± 59 ms by the sixth week. For T2, the results were 171 ± 10 ms and 128 ± 12 ms, respectively.
Postpartum Oxytocin Treatment via the Mother Reprograms Long-Term Behavioral Disorders Induced by Early Life Stress on the Plasma and Brain Metabolome in the Rat
Authors: Morley-Fletcher Sara , Gaetano Alessandra , Gao Vance , Gatta Eleonora , Van Camp Gilles , Bouwalerh Hammou , Thomas Pierre , Nicoletti Ferdinando , Maccari Stefania
Published: March 2024

The rat model of perinatal stress (PRS), in which exposure of pregnant dams to restraint stress reduces maternal behavior, is characterized by a metabolic profile that is reminiscent of the “metabolic syndrome”. We aimed to identify plasma metabolomic signatures linked to long-term programming induced by PRS in aged male rats. This study was conducted in the plasma and frontal cortex. We also investigated the reversal effect of postpartum carbetocin (Cbt) on these signatures, along with its impact on deficits in cognitive, social, and exploratory behavior. We found that PRS induced long-lasting changes in biomarkers of secondary bile acid metabolism in the plasma and glutathione metabolism in the frontal cortex. Cbt treatment demonstrated disease-dependent effects by reversing the metabolite alterations. The metabolomic signatures of PRS were associated with long-term cognitive and emotional alterations alongside endocrinological disturbances. Our findings represent the first evidence of how early life stress may alter the metabolomic profile in aged individuals, thereby increasing vulnerability to CNS disorders. This raises the intriguing prospect that the pharmacological activation of oxytocin receptors soon after delivery through the mother may rectify these alterations.
Gene Expression of CSF3R/CD114 Is Associated with Poorer Patient Survival in Glioma
Authors: Bark Samir Ale , Dalmolin Matheus , Malafaia Osvaldo , Roesler Rafael , Fernandes Marcelo A. C. , Isolan Gustavo R.
Published: March 2024

Gliomas comprise most cases of central nervous system (CNS) tumors. Gliomas afflict both adults and children, and glioblastoma (GBM) in adults represents the clinically most important type of malignant brain cancer, with a very poor prognosis. The cell surface glycoprotein CD114, which is encoded by the CSF3R gene, acts as the receptor for the granulocyte colony stimulating factor (GCSF), and is thus also called GCSFR or CSFR. CD114 is a marker of cancer stem cells (CSCs), and its expression has been reported in several cancer types. In addition, CD114 may represent one among various cases where brain tumors hijack molecular mechanisms involved in neuronal survival and synaptic plasticity. Here, we describe CSF3R mRNA expression in human gliomas and their association with patient prognosis as assessed by overall survival (OS). We found that the levels of CSF3R/CD114 transcripts are higher in a few different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and GBM, in comparison to non-tumoral neural tissue. We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM.
Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus
Authors: Carrión-Barberà Irene , Triginer Laura , Tío Laura , Pérez-García Carolina , Ribes Anna , Abad Victoria , Pros Ana , Bermúdez-López Marcelino , Castro-Boqué Eva , Lecube Albert , Valdivielso José Manuel ,   ILERVAS Project Group, Monfort Jordi , Salman-Monte Tarek Carlos
Published: March 2024

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients’ data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.
Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection
Authors: Seal Anouska , Hughes Megan , Wei Fei , Pugazhendhi Abinaya S. , Ngo Christopher , Ruiz Jonathan , Schwartzman Jonathan D. , Coathup Melanie J.
Published: March 2024

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.
Neutrophil Extracellular DNA Traps in Response to Infection or Inflammation, and the Roles of Platelet Interactions
Authors: Chen William A. , Boskovic Danilo S.
Published: March 2024

Neutrophils present the host’s first line of defense against bacterial infections. These immune effector cells are mobilized rapidly to destroy invading pathogens by (a) reactive oxygen species (ROS)-mediated oxidative bursts and (b) via phagocytosis. In addition, their antimicrobial service is capped via a distinct cell death mechanism, by the release of their own decondensed nuclear DNA, supplemented with a variety of embedded proteins and enzymes. The extracellular DNA meshwork ensnares the pathogenic bacteria and neutralizes them. Such neutrophil extracellular DNA traps (NETs) have the potential to trigger a hemostatic response to pathogenic infections. The web-like chromatin serves as a prothrombotic scaffold for platelet adhesion and activation. What is less obvious is that platelets can also be involved during the initial release of NETs, forming heterotypic interactions with neutrophils and facilitating their responses to pathogens. Together, the platelet and neutrophil responses can effectively localize an infection until it is cleared. However, not all microbial infections are easily cleared. Certain pathogenic organisms may trigger dysregulated platelet–neutrophil interactions, with a potential to subsequently propagate thromboinflammatory processes. These may also include the release of some NETs. Therefore, in order to make rational intervention easier, further elucidation of platelet, neutrophil, and pathogen interactions is still needed.
Domain-Specific Dictionary between Human and Machine Languages
Authors: Islam Md Saiful , Liu Fei
Published: March 2024

In the realm of artificial intelligence, knowledge graphs have become an effective area of research. Relationships between entities are depicted through a structural framework in knowledge graphs. In this paper, we propose to build a domain-specific medicine dictionary (DSMD) based on the principles of knowledge graphs. Our dictionary is composed of structured triples, where each entity is defined as a concept, and these concepts are interconnected through relationships. This comprehensive dictionary boasts more than 348,000 triples, encompassing over 20,000 medicine brands and 1500 generic medicines. It presents an innovative method of storing and accessing medical data. Our dictionary facilitates various functionalities, including medicine brand information extraction, brand-specific queries, and queries involving two words or question answering. We anticipate that our dictionary will serve a broad spectrum of users, catering to both human users, such as a diverse range of healthcare professionals, and AI applications.
Advances in Additive Friction Extrusion Deposition (AFED): Process and Tool Design
Authors: Hossfeld Max , Wright Arnold
Published: March 2024

Additive friction extrusion deposition (AFED) is a recently developed additive manufacturing technique that promises high deposition rates at low forces. Due to the novelty of the process, the underlying phenomena and their interactions are not fully understood, and in particular, the processing strategy and tool design are still in their infancy. This work contributes to the state-of-the-art of AFED through a comprehensive analysis of its working principles and an experimental program, including a representative sample component. The working principle and process mechanics of AFED are broken down into their individual components. The forces and their origins and effects on the process are described, and measures of process efficiency and theoretical minimum energy consumption are derived. Three geometrical features of the extrusion die were identified as most relevant to the active material flow, process forces, and deposition quality: the topography of the inner and outer circular surfaces and the geometry of its extrusion channels. Based on this, the experimental program investigated seven different tool designs in terms of efficiency, force reduction, and throughput. The experiments using AA 6061-T6 as feedstock show that AFED is capable of both high material throughput (close to 550 mm3/s) and reduced substrate forces, for example, the forces for a run at 100 mm3/s remained continuously below 500 N and for a run at 400 mm3/s below 3500 N. The material flow and microstructure of AFED were assessed from macro-sections. Significant differences were found between the advancing and retracting sides for both process effects and material flow. Banded structures in the microstructure show strong similarities to other solid-state processes. The manufacturing of the sample components demonstrates that AFED is already capable of producing industrial-grade components. In mechanical tests, interlayer bonding defects resulted in more brittle failure behavior in the build direction of the structure, whereas in the horizontal direction, mechanical properties corresponding to a T4 temper were achieved.
Interactions of Low-Energy Muons with Silicon: Numerical Simulation of Negative Muon Capture and Prospects for Soft Errors
Authors: Autran Jean-Luc , Munteanu Daniela
Published: March 2024

In this paper, the interactions of low-energy muons (E < 10 MeV) with natural silicon, the basic material of microelectronics, are studied by Geant4 and SRIM simulation. The study is circumscribed to muons susceptible to slowdown/stop in the target and able to transfer sufficient energy to the semiconductor to create single events in silicon devices or related circuits. The capture of negative muons by silicon atoms is of particular interest, as the resulting nucleus evaporation and its effects can be catastrophic in terms of the emission of secondary ionizing particles ranging from protons to aluminum ions. We investigate in detail these different nuclear capture reactions in silicon and quantitatively evaluate their relative importance in terms of number of products, energy, linear energy transfer, and range distributions, as well as in terms of charge creation in silicon. Finally, consequences in the domain of soft errors in microelectronics are discussed.
Who Are the Online Medication Shoppers? A Market Segmentation of the Swedish Welfare State
Authors: Roos John Magnus , Jansson Magnus , Bjerkeli Pernilla J.
Published: March 2024

The present study aimed to explore the online shopping of medicines from demographic, geographic, psychographic, and behavioral factors. A quantitative survey design was used with a quote sample representing the Swedish population regarding age, gender, and residential area. In total, 1863 persons responded to a survey, including measures of age, gender, income, education, area of residence, personality traits (BFI-10), values (Rokeach Value Survey), self-estimated health-status, internet usage, online shopping in general, and online shopping of medicines. Firstly, the data were analyzed with chi-squares and independent t-tests. From these initial analyses, online shopping of medicines was associated with young age, female gender, high income and education, living in a big city, extraversion, several values of desirable end-states of existence (e.g., self-respect, a sense of accomplishment, and pleasure), internet usage, and general online shopping. Secondly, the significant (p < 0.05) variables from the initial analysis were included in a logistic regression analysis. This comprehensive model showed that online medication shoppers are best predicted by being female and the use of internet. Unlike what was previously known about medication shoppers, the typical online medication shopper appears to be driven by hedonistic values and self-actualization, rather than health status. We suggest that further research replicate this study outside and inside Sweden, and that health status is measured in a different way.