bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of Deep Learning-Based Lightning Prediction
Authors: Wang Xupeng , Hu Keyong , Wu Yongling , Zhou Wei
Published: November 2023

The escalation of climate change and the increasing frequency of extreme weather events have amplified the importance of precise and timely lightning prediction. This predictive capability is pivotal for the preservation of life, protection of property, and maintenance of crucial infrastructure safety. Recently, the rapid advancement and successful application of data-driven deep learning across diverse sectors, particularly in computer vision and spatio-temporal data analysis, have opened up innovative avenues for enhancing both the accuracy and efficiency of lightning prediction. This article presents a comprehensive review of the broad spectrum of existing lightning prediction methodologies. Starting from traditional numerical forecasting techniques, the path to the most recent breakthroughs in deep learning research are traversed. For these diverse methods, we shed light on their progression and summarize their capabilities, while also predicting their future development trajectories. This exploration is designed to enhance understanding of these methodologies to better utilize their strengths, navigate their limitations, and potentially integrate these techniques to create novel and powerful lightning prediction tools. Through such endeavors, the aim is to bolster preparedness against the growing unpredictability of climate and ensure a proactive stance towards lightning prediction.
The Frequency of Extreme Cold Events in North China and Their Relationship with Sea Surface Temperature Anomalies
Authors: Yang Na , Li Liping , Ren Yike , Ni Wenjie , Liu Lu
Published: November 2023

This study investigated the interdecadal characteristics of the frequency of the winter single station extreme cold events (SSECEs) in North China and their relationship with sea surface temperature (SST). The results showed the following: (a) The SSECEs occurred frequently before 1991, but less thereafter, with an increase after 2018. The first two interdecadal modes of the SSECE frequency were east–west inverse and “n” patterns. (b) The interdecadal abrupt change of the “n” pattern occurred around 1997/1998. Before 1997/1998, the synergistic effects between the positive Interdecadal Pacific Oscillation (+IPO) and the negative North Atlantic Multidecadal Oscillation (−AMO) triggered the “two troughs and one ridge” anomalous circulation in Eurasia. The Rossby wave energy propagated downstream from the Atlantic, strengthening the Lake Baikal ridge. Furthermore, the Siberian High (SH) became weaker in the north and stronger in the south. With the favorable jet conditions, the cold air invaded North China along the northerly airflow in front of the Lake Baikal ridge, resulting in the frequent SSECE occurrence in central North China. Afterwards, the opposite occurred. (c) The cooperation of SST anomalies (SSTAs) led to the east–west inverse anomaly of the SSECE frequency. Before 1991, the high SSTAs in the central North Atlantic and low SSTAs in the equatorial Indian Ocean and the southwest Pacific triggered “+”, “−”, “+”, and “−” wave trains at mid-latitudes from the Atlantic to the North Pacific. The Rossby wave energy propagated eastward from the Atlantic, resulting in the SH and Urals ridge strengthening, and the Aleutian Low and East Asian trough deepening. The northwestern airflow in front of the Urals ridge guided the cold air into North China, leading to frequent SSECEs in central and eastern North China before 1991. The opposite occurred between 1992 and 2018.
New Two-Level Time-Mesh Difference Scheme for the Symmetric Regularized Long Wave Equation
Authors: Gao Jingying , Bai Qingmei , He Siriguleng , Buhe Eerdun
Published: November 2023

The paper introduces a new two-level time-mesh difference scheme for solving the symmetric regularized long wave equation. The scheme consists of three steps. A coarse time-mesh and a fine time-mesh are defined, and the equation is solved using an existing nonlinear scheme on the coarse time-mesh. Lagrange’s linear interpolation formula is employed to obtain all preliminary solutions on the fine time-mesh. Based on the preliminary solutions, Taylor’s formula is utilized to construct a linear system for the equation on the fine time-mesh. The convergence and stability of the scheme is analyzed, providing the convergence rates of O(τF2+τC4+h4) in the discrete L∞-norm for u(x,t) and in the discrete L2-norm for ρ(x,t). Numerical simulation results show that the proposed scheme achieves equivalent error levels and convergence rates to the nonlinear scheme, while also reducing CPU time by over half, which indicates that the new method is more efficient. Furthermore, compared to the earlier time two-mesh method developed by the authors, the proposed scheme significantly reduces the error between the numerical and exact solutions, which means that the proposed scheme is more accurate. Additionally, the effectiveness of the new scheme is discussed in terms of the corresponding conservation laws and long-time simulations.
The Juvenile-Hormone-Responsive Factor AmKr-h1 Regulates Caste Differentiation in Honey Bees
Authors: Gong Zhi-Xian , Cheng Fu-Ping , Xu Jia-Ning , Yan Wei-Yu , Wang Zi-Long
Published: November 2023

Honey bees are typical model organisms for the study of caste differentiation, and the juvenile hormone (JH) is a crucial link in the regulatory network of caste differentiation in honey bees. To investigate the mechanism of JH-mediated caste differentiation, we analyzed the effect of the JH response gene AmKr-h1 on this process. We observed that AmKr-h1 expression levels were significantly higher in queen larvae than in worker larvae at the 48 h, 84 h, and 120 h larval stages, and were regulated by JH. Inhibiting AmKr-h1 expression in honey bee larvae using RNAi could lead to the development of larvae toward workers. We also analyzed the transcriptome changes in honey bee larvae after AmKr-h1 RNAi and identified 191 differentially expressed genes (DEGs) and 682 differentially expressed alternative splicing events (DEASEs); of these, many were related to honey bee caste differentiation. Our results indicate that AmKr-h1 regulates caste differentiation in honey bees by acting as a JH-responsive gene.
Dopamine-Depleted Dopamine Transporter Knockout (DDD) Mice: Dyskinesia with L-DOPA and Dopamine D1 Agonists
Authors: Pogorelov Vladimir M. , Martini Michael L. , Jin Jian , Wetsel William C. , Caron Marc G.
Published: November 2023

L-DOPA is the mainstay of treatment for Parkinson’s disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dopamine-transporter KO (DDD) mice. Treatment with α-methyl-para-tyrosine rapidly depletes their brain stores of DA and renders them akinetic. During sensitization in the open field (OF), their locomotion declines as vertical activities increase and upon encountering a wall they stand on one leg or tail and engage in climbing behavior termed “three-paw dyskinesia”. We have hypothesized that L-DOPA induces a stereotypic activation of locomotion in DDD mice, where they are unable to alter the course of their locomotion, and upon encountering walls engage in “three-paw dyskinesia” as reflected in vertical counts or beam-breaks. The purpose of our studies was to identify a valid index of LID in DDD mice that met three criteria: (a) sensitization with repeated L-DOPA administration, (b) insensitivity to a change in the test context, and (c) stimulatory or inhibitory responses to dopamine D1 receptor agonists (5 mg/kg SKF81297; 5 and 10 mg/kg MLM55-38, a novel compound) and amantadine (45 mg/kg), respectively. Responses were compared between the OF and a circular maze (CM) that did not hinder locomotion. We found vertical counts and climbing were specific for testing in the OF, while oral stereotypies were sensitized to L-DOPA in both the OF and CM and responded to D1R agonists and amantadine. Hence, in DDD mice oral stereotypies should be used as an index of LID in screening compounds for PD.
LEO1 Is Required for Efficient Entry into Quiescence, Control of H3K9 Methylation and Gene Expression in Human Fibroblasts
Authors: Laurent Marc , Cordeddu Lina , Zahedi Yasaman , Ekwall Karl
Published: November 2023

(1) Background: The LEO1 (Left open reading frame 1) protein is a conserved subunit of the PAF1C complex (RNA polymerase II-associated factor 1 complex). PAF1C has well-established mechanistic functions in elongation of transcription and RNA processing. We previously showed, in fission yeast, that LEO1 controls histone H3K9 methylation levels by affecting the turnover of histone H3 in chromatin, and that it is essential for the proper regulation of gene expression during cellular quiescence. Human fibroblasts enter a reversible quiescence state upon serum deprivation in the growth media. Here we investigate the function of LEO1 in human fibroblasts. (2) Methods: We knocked out the LEO1 gene using CRISPR/Cas9 methodology in human fibroblasts and verified that the LEO1 protein was undetectable by Western blot. We characterized the phenotype of the ΔLEO1 knockout cells with FACS analysis and cell growth assays. We used RNA-sequencing using spike-in controls to measure gene expression and spike-in controlled ChIP-sequencing experiments to measure the histone modification H3K9me2 genome-wide. (3) Results: Gene expression levels are altered in quiescent cells, however factors controlling chromatin and gene expression changes in quiescent human cells are largely unknown. The ΔLEO1 knockout fibroblasts are viable but have reduced metabolic activity compared to wild-type cells. ΔLEO1 cells showed a slower entry into quiescence and a different morphology compared to wild-type cells. Gene expression was generally reduced in quiescent wild-type cells. The downregulated genes included genes involved in cell proliferation. A small number of genes were upregulated in quiescent wild-type cells including several genes involved in ERK1/ERK2 and Wnt signaling. In quiescent ΔLEO1 cells, many genes were mis-regulated compared to wild-type cells. This included genes involved in Calcium ion transport and cell morphogenesis. Finally, spike-in controlled ChIP-sequencing experiments demonstrated that the histone modification H3K9me2 levels are globally increased in quiescent ΔLEO1 cells. (4) Conclusions: Thus, LEO1 is important for proper entry into cellular quiescence, control of H3K9me2 levels, and gene expression in human fibroblasts.
Why Intracranial Compliance Is Not Utilized as a Common Practical Tool in Clinical Practice
Authors: Gholampour Seifollah
Published: November 2023

Intracranial compliance (ICC) holds significant potential in neuromonitoring, serving as a diagnostic tool and contributing to the evaluation of treatment outcomes. Despite its comprehensive concept, which allows consideration of changes in both volume and intracranial pressure (ICP), ICC monitoring has not yet established itself as a standard component of medical care, unlike ICP monitoring. This review highlighted that the first challenge is the assessment of ICC values, because of the invasive nature of direct measurement, the time-consuming aspect of non-invasive calculation through computer simulations, and the inability to quantify ICC values in estimation methods. Addressing these challenges is crucial, and the development of a rapid, non-invasive computer simulation method could alleviate obstacles in quantifying ICC. Additionally, this review indicated the second challenge in the clinical application of ICC, which involves the dynamic and time-dependent nature of ICC. This was considered by introducing the concept of time elapsed (TE) in measuring the changes in volume or ICP in the ICC equation (volume change/ICP change). The choice of TE, whether short or long, directly influences the ICC values that must be considered in the clinical application of the ICC. Compensatory responses of the brain exhibit non-monotonic and variable changes in long TE assessments for certain disorders, contrasting with the mono-exponential pattern observed in short TE assessments. Furthermore, the recovery behavior of the brain undergoes changes during the treatment process of various brain disorders when exposed to short and long TE conditions. The review also highlighted differences in ICC values across brain disorders with various strain rates and loading durations on the brain, further emphasizing the dynamic nature of ICC for clinical application. The insight provided in this review may prove valuable to professionals in neurocritical care, neurology, and neurosurgery for standardizing ICC monitoring in practical application related to the diagnosis and evaluation of treatment outcomes in brain disorders.
An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches
Authors: Irfan Ali , Faisal Shah , Ahmad Sajjad , Saif Muhammad Jawwad , Zahoor Ameer Fawad , Khan Samreen Gul , Javid Jamila , Al-Hussain Sami A. , Muhammed Muhammed Tilahun , Zaki Magdi E. A.
Published: November 2023

Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole BF1–BF7 and benzofuran-1,2,4-triazole compounds BF8–BF15 were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole BF1–BF15 molecules. Benzofuran-1,3,4-oxadiazole scaffolds BF1–BF7 showed lesser binding affinities (−12.63 to −14.04 Kcal/mol) than benzofuran-1,2,4-triazole scaffolds BF8–BF15 (−14.11 to −16.09 Kcal/mol) against the HCV NS5B enzyme. Molecular docking studies revealed the excellent binding affinity scores exhibited by benzofuran-1,2,4-triazole structural motifs BF-9 (−16.09 Kcal/mol), BF-12 (−15.75 Kcal/mol), and BF-13 (−15.82 Kcal/mol), respectively, which were comparatively better than benzofuran-based HCV NS5B inhibitors’ standard reference drug Nesbuvir (−15.42 Kcal/mol). A molecular dynamics simulation assay was also conducted to obtain valuable insights about the enzyme–compounds interaction profile and structural stability, which indicated the strong intermolecular energies of the BF-9+NS5B complex and the BF-12+NS5B complex as per the MM-PBSA method, while the BF-12+NS5B complex was the most stable system as per the MM-GBSA calculation. The drug-likeness and ADMET studies of all the benzofuran-1,2,4-triazole derivatives BF8–BF15 revealed that these compounds possessed good medicinal chemistry profiles in agreement with all the evaluated parameters for being drugs. The molecular docking affinity scores, MM-PBSA/MM-GBSA and MD-simulation stability analysis, drug-likeness profiling, and ADMET study assessment indicated that N-4-fluorophenyl-S-linked benzofuran-1,2,4-triazole BF-12 could be a future promising anti-HCV NS5B RdRp inhibitor therapeutic drug candidate that has a structural agreement with the Nesbuvir standard reference drug.
Brittle Asthma: Still on Board?
Authors: Visca Dina , Ardesi Francesco , Centis Rosella , Pignatti Patrizia , Spanevello Antonio
Published: November 2023

(1) Background: “Brittle Asthma” was considered an asthma clinical phenotype and deemed to be life-threatening in the early 2000s; then, this definition disappeared. The purpose of this review is to examine what has historically been referred to as this term and see whether it may be applied to modern clinical practice, thus acquiring fresh relevance and meaning. (2) Methods: A non-systematic search of the literature was conducted using both MeSH and free-text phrases. No limitations on the research design or type of publication were applied. (3) Results: Reliable data regarding “Brittle Asthma” are lacking due to the paucity of current data and the few studies available. After a few years of reworking, it was divided into two sub-classes: one characterized by a wide PEF variability despite high-dose therapy and the other by sudden acute attacks in otherwise apparently normal airway functions or well-controlled asthma. Their characteristics were hardly defined because of their low prevalence. Data regarding risk factors, atopy, mechanisms, and treatments were analyzed. (4) Conclusions: Over time, different terminology has been introduced to define asthma severity and control. It would be worth investigating whether the term “Brittle Asthma” previously used may be helpful to find new hints to stratify patients and improve disease management.
An Optimized Model Based on Deep Learning and Gated Recurrent Unit for COVID-19 Death Prediction
Authors: Tarek Zahraa , Shams Mahmoud Y. , Towfek S. K. , Alkahtani Hend K. , Ibrahim Abdelhameed , Abdelhamid Abdelaziz A. , Eid Marwa M. , Khodadadi Nima , Abualigah Laith , Khafaga Doaa Sami , Elshewey Ahmed M.
Published: November 2023

The COVID-19 epidemic poses a worldwide threat that transcends provincial, philosophical, spiritual, radical, social, and educational borders. By using a connected network, a healthcare system with the Internet of Things (IoT) functionality can effectively monitor COVID-19 cases. IoT helps a COVID-19 patient recognize symptoms and receive better therapy more quickly. A critical component in measuring, evaluating, and diagnosing the risk of infection is artificial intelligence (AI). It can be used to anticipate cases and forecast the alternate incidences number, retrieved instances, and injuries. In the context of COVID-19, IoT technologies are employed in specific patient monitoring and diagnosing processes to reduce COVID-19 exposure to others. This work uses an Indian dataset to create an enhanced convolutional neural network with a gated recurrent unit (CNN-GRU) model for COVID-19 death prediction via IoT. The data were also subjected to data normalization and data imputation. The 4692 cases and eight characteristics in the dataset were utilized in this research. The performance of the CNN-GRU model for COVID-19 death prediction was assessed using five evaluation metrics, including median absolute error (MedAE), mean absolute error (MAE), root mean squared error (RMSE), mean square error (MSE), and coefficient of determination (R2). ANOVA and Wilcoxon signed-rank tests were used to determine the statistical significance of the presented model. The experimental findings showed that the CNN-GRU model outperformed other models regarding COVID-19 death prediction.
Alzheimer’s Disease Biomarker Detection Using Field Effect Transistor-Based Biosensor
Authors: Le Phan Gia , Choi Seong Hye , Cho Sungbo
Published: November 2023

Alzheimer’s disease (AD) is closely related to neurodegeneration, leading to dementia and cognitive impairment, especially in people aged > 65 years old. The detection of biomarkers plays a pivotal role in the diagnosis and treatment of AD, particularly at the onset stage. Field-effect transistor (FET)-based sensors are emerging devices that have drawn considerable attention due to their crucial ability to recognize various biomarkers at ultra-low concentrations. Thus, FET is broadly manipulated for AD biomarker detection. In this review, an overview of typical FET features and their operational mechanisms is described in detail. In addition, a summary of AD biomarker detection and the applicability of FET biosensors in this research field are outlined and discussed. Furthermore, the trends and future prospects of FET devices in AD diagnostic applications are also discussed.
Effect of Chronic Ankle Instability on the Biomechanical Organization of Gait Initiation: A Systematic Review
Authors: Yousefi Mohammad , Zivari Shaghayegh , Yiou Eric , Caderby Teddy
Published: November 2023

This systematic review was conducted to provide an overview of the effects of chronic ankle instability (CAI) on the biomechanical organization of gait initiation. Gait initiation is a classical model used in the literature to investigate postural control in healthy and pathological individuals. PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar were searched for relevant articles. Eligible studies were screened and data extracted by two independent reviewers. An evaluation of the quality of the studies was performed using the Downs and Black checklist. A total of 878 articles were found in the initial search, but only six studies met the inclusion criteria. The findings from the literature suggest that CAI affects the characteristics of gait initiation. Specifically, individuals with CAI exhibit notable differences in reaction time, the spatiotemporal parameters of anticipatory postural adjustments (APAs) and step execution, ankle–foot kinematics, and muscle activation compared to healthy controls. In particular, the observed differences in APA patterns associated with gait initiation suggest the presence of supraspinal motor control alterations in individuals with CAI. These findings may provide valuable information for the rehabilitation of these patients. However, the limited evidence available calls for caution in interpreting the results and underscores the need for further research.
Gait Domains May Be Used as an Auxiliary Diagnostic Index for Alzheimer’s Disease
Authors: Duan Qi , Zhang Yinuo , Zhuang Weihao , Li Wenlong , He Jincai , Wang Zhen , Cheng Haoran
Published: November 2023

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cognitive dysfunction and behavioral impairment. We aimed to use principal components factor analysis to explore the association between gait domains and AD under single and dual-task gait assessments. Methods: A total of 41 AD participants and 41 healthy control (HC) participants were enrolled in our study. Gait parameters were measured using the JiBuEn® gait analysis system. The principal component method was used to conduct an orthogonal maximum variance rotation factor analysis of quantitative gait parameters. Multiple logistic regression was used to adjust for potential confounding or risk factors. Results: Based on the factor analysis, three domains of gait performance were identified both in the free walk and counting backward assessments: “rhythm” domain, “pace” domain and “variability” domain. Compared with HC, we found that the pace factor was independently associated with AD in two gait assessments; the variability factor was independently associated with AD only in the counting backwards assessment; and a statistical difference still remained after adjusting for age, sex and education levels. Conclusions: Our findings indicate that gait domains may be used as an auxiliary diagnostic index for Alzheimer’s disease.
Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings
Authors: Begagić Emir , Pugonja Ragib , Bečulić Hakija , Čeliković Amila , Tandir Lihić Lejla , Kadić Vukas Samra , Čejvan Lejla , Skomorac Rasim , Selimović Edin , Jaganjac Belma , Juković-Bihorac Fatima , Jusić Aldin , Pojskić Mirza
Published: November 2023

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management.
Determinants of Continuous Usage Intention in Community Group Buying Platform in China: Based on the Information System Success Model and the Expanded Technology Acceptance Model
Authors: Song Yingjie , Gui Lin , Wang Hong , Yang Yanru
Published: November 2023

Community group buying is a new retail model with broad development prospects. The community group buying model in China has brought obvious social and economic benefits. However, the continuous usage rate on some community group buying platforms is relatively low. Consumers’ continuous usage intentions are closely related to the sustainable development of community group buying platforms. Therefore, this study integrates the information system success model (D&M model) and the expanded technology acceptance model (TAM) to construct a research model that explores the factors influencing consumers’ continuous usage intentions from both the platform’s and consumers’ perspectives. The survey data involving 418 respondents who used community group buying platforms were developed and analyzed for structural equation model (SEM) testing. The results show the following: (1) Perceived usefulness, perceived ease of use, service quality, perceived trust, expectation confirmation, and subjective norms significantly affect continuous usage intention. (2) Subjective norms are significantly related to continuous usage intention. Perceived usefulness, perceived ease of use, service quality, perceived trust, and expectation confirmation indirectly affect continuous usage intention through user satisfaction. This research provides a new perspective for the theoretical research of community group buying and helps to promote the sustainable development of community group buying platforms in management practice.
Perinatal Depression and the Role of Synaptic Plasticity in Its Pathogenesis and Treatment
Authors: Shenoy Sonia , Ibrahim Sufyan
Published: November 2023

Emerging evidence indicates that synaptic plasticity is significantly involved in the pathophysiology and treatment of perinatal depression. Animal models have demonstrated the effects of overstimulated or weakened synapses in various circuits of the brain in causing affective disturbances. GABAergic theory of depression, stress, and the neuroplasticity model of depression indicate the role of synaptic plasticity in the pathogenesis of depression. Multiple factors related to perinatal depression like hormonal shifts, newer antidepressants, mood stabilizers, monoamine systems, biomarkers, neurotrophins, cytokines, psychotherapy and electroconvulsive therapy have demonstrated direct and indirect effects on synaptic plasticity. In this review, we discuss and summarize the various patho-physiology-related effects of synaptic plasticity in depression. We also discuss the association of treatment-related aspects related to psychotropics, electroconvulsive therapy, neuromodulation, psychotherapy, physical exercise and yoga with synaptic plasticity in perinatal depression. Future insights into newer methods of treatment directed towards the modulation of neuroplasticity for perinatal depression will be discussed.
Exploring the Link between Interoceptive Body Awareness and Suicidal Orientation in University Students: A Cross-Sectional Study
Authors: Montoya-Hurtado Olga Lucia , Gómez-Jaramillo Nicolás , Criado-Gutiérrez José María , Pérez Jesús , Sancho-Sánchez Consuelo , Sánchez-Barba Mercedes , Tejada-Garrido Clara Isabel , Criado-Pérez Laura , Sánchez-González Juan Luis , Santolalla-Arnedo Iván , del Pozo-Herce Pablo , Juárez-Vela Raúl
Published: November 2023

Introduction: The transition to college life can impact the mental health of students. There are mental health care strategies that promote connection with the body’s internal signals, which can help to improve mental well-being, manage emotions, and reduce the risk of suicide in university students. Aim: This study aimed to examine the association between interoceptive body awareness variables and suicidal orientation in a sample of 169 undergraduate students in Colombia. Methods: An observational, cross-sectional study was conducted in 2023 with Colombian students as the participants. Results: The findings revealed a significant and moderately negative correlation between the Multidimensional Assessment of Interoceptive Awareness (MAIA) total score and the Inventory of Suicide Orientation (ISO-30) total score (r = −0.54, p < 0.001). Confidence and self-regulation were identified as the most influential factors in the relationship between MAIA and ISO-30. Significant correlations were observed (p < 0.001), indicating moderate correlation values ranging from −0.43 to −0.57. Discussion: Our findings support the existence of a negative correlation between interoceptive body awareness and suicidal orientation. Further research is needed to better understand this relationship and to develop specific interventions based on body awareness to prevent suicide orientation. Conclusion: There are practical implications associated with recognizing the importance of body awareness in relation to decreasing suicidal orientation, and multidisciplinary teams addressing mental health can incorporate this knowledge.
Empathy Modulates the Activity of the Sensorimotor Mirror Neuron System during Pain Observation
Authors: Plata-Bello Julio , Privato Nicole , Modroño Cristián , Pérez-Martín Yaiza , Borges África , González-Mora José Luis
Published: November 2023

Aim: The aim of this study is to analyze the brain activity patterns during the observation of painful expressions and to establish the relationship between this activity and the scores obtained on the Interpersonal Reactivity Index (IRI). Methods: The study included twenty healthy, right-handed subjects (10 women). We conducted a task-based and resting-state functional magnetic resonance imaging (fMRI) study. The task involved observing pictures displaying painful expressions. We performed a region of interest (ROI) analysis focusing on the core regions of the sensorimotor mirror neuron system (MNS). Resting-state fMRI was utilized to assess the functional connectivity of the sensorimotor MNS regions with the rest of the cortex using a seed-to-voxel approach. Additionally, we conducted a regression analysis to examine the relationship between brain activity and scores from the IRI subtests. Results: Observing painful expressions led to increased activity in specific regions of the frontal, temporal, and parietal lobes. The largest cluster of activation was observed in the left inferior parietal lobule (IPL). However, the ROI analysis did not reveal any significant activity in the remaining core regions of the sensorimotor MNS. The regression analysis demonstrated a positive correlation between brain activity during the observation of pain and the “empathic concern” subtest scores of the IRI in both the cingulate gyri and bilateral IPL. Finally, we identified a positive relationship between the “empathic concern” subtest of the IRI and the functional connectivity (FC) of bilateral IPLs with the bilateral prefrontal cortex and the right IFG. Conclusion: Observing expressions of pain triggers activation in the sensorimotor MNS, and this activation is influenced by the individual’s level of empathy.
Direct Tensile Capacity of Steel-Tube Connections in a Precast Concrete Double-Wall System
Authors: Meiramov Didar , Seo Yujae , Ju Hyunjin , Cho Hae-Chang
Published: November 2023

This study introduces a new precast concrete (PC) double-wall system designed to simplify the complex fabrication process of existing PC double-wall systems and eliminate laitance and other defects that can occur during the manufacture of concrete panels. An experiment and finite element analysis were conducted on 11 specimens to determine the tensile resistance performance of rectangular steel tubes that maintain spacing to avoid damage to the PC panels during transportation or on-site installation. Specimens varied in terms of the end details of the rectangular steel tubes, such as the presence of welded steel plates or embedded concrete and total length in terms of whether longer or shorter specimens were used. As a result, the specimens showed a 20–30% increase in maximum tensile strength compared to the control specimen according to the end details, except for the case where side steel plates were cut and bent inward. The control specimen filled with concrete was the most suitable for connections when constructing PC double-wall systems. It has significant tensile resistance according to the experiment and finite element analysis and does not require additional construction steps or costs.
The Development and External Validation of Artificial Intelligence-Driven MRI-Based Models to Improve Prediction of Lesion-Specific Extraprostatic Extension in Patients with Prostate Cancer
Authors: van den Berg Ingeborg , Soeterik Timo F. W. , van der Hoeven Erik J. R. J. , Claassen Bart , Brink Wyger M. , Baas Diederik J. H. , Sedelaar J. P. Michiel , Heine Lizette , Tol Jim , van der Voort van Zyp Jochem R. N. , van den Berg Cornelis A. T. , van den Bergh Roderick C. N. , van Basten Jean-Paul A. , van Melick Harm H. E.
Published: November 2023

Adequate detection of the histopathological extraprostatic extension (EPE) of prostate cancer (PCa) remains a challenge using conventional radiomics on 3 Tesla multiparametric magnetic resonance imaging (3T mpMRI). This study focuses on the assessment of artificial intelligence (AI)-driven models with innovative MRI radiomics in predicting EPE of prostate cancer (PCa) at a lesion-specific level. With a dataset encompassing 994 lesions from 794 PCa patients who underwent robot-assisted radical prostatectomy (RARP) at two Dutch hospitals, the study establishes and validates three classification models. The models were validated on an internal validation cohort of 162 lesions and an external validation cohort of 189 lesions in terms of discrimination, calibration, net benefit, and comparison to radiology reporting. Notably, the achieved AUCs ranged from 0.86 to 0.91 at the lesion-specific level, demonstrating the superior accuracy of the random forest model over conventional radiological reporting. At the external test cohort, the random forest model was the best-calibrated model and demonstrated a significantly higher accuracy compared to radiological reporting (83% vs. 67%, p = 0.02). In conclusion, an AI-powered model that includes both existing and novel MRI radiomics improves the detection of lesion-specific EPE in prostate cancer.
Revealing Pan-Histology Immunomodulatory Targets in Pediatric Central Nervous System Tumors
Authors: Galvin Robert T. , Jena Sampreeti , Maeser Danielle , Gruener Robert , Huang R. Stephanie
Published: November 2023

Background: The application of immunotherapy for pediatric CNS malignancies has been limited by the poorly understood immune landscape in this context. The aim of this study was to uncover the mechanisms of immune suppression common among pediatric brain tumors. Methods: We apply an immunologic clustering algorithm validated by The Cancer Genome Atlas Project to an independent pediatric CNS transcriptomic dataset. Within the clusters, the mechanisms of immunosuppression are explored via tumor microenvironment deconvolution and survival analyses to identify relevant immunosuppressive genes with translational relevance. Results: High-grade diseases fall predominantly within an immunosuppressive subtype (C4) that independently lowers overall survival time and where common immune checkpoints (e.g., PDL1, CTLA4) are less relevant. Instead, we identify several alternative immunomodulatory targets with relevance across histologic diseases. Specifically, we show how the mechanism of EZH2 inhibition to enhance tumor immunogenicity in vitro via the upregulation of MHC class 1 is applicable to a pediatric CNS oncologic context. Meanwhile, we identify that the C3 (inflammatory) immune subtype is more common in low-grade diseases and find that immune checkpoint inhibition may be an effective way to curb progression for this subset. Conclusions: Three predominant immunologic clusters are identified across pediatric brain tumors. Among high-risk diseases, the predominant immune cluster is associated with recurrent immunomodulatory genes that influence immune infiltrate, including a subset that impacts survival across histologies.
Potential Tumor Suppressor Role of Polo-like Kinase 5 in Cancer
Authors: Su Shengqin , Ndiaye Mary Ann , Guzmán-Pérez Glorimar , Baus Rebecca Michael , Huang Wei , Patankar Manish Suresh , Ahmad Nihal
Published: November 2023

The polo-like kinase (PLK) family of serine/threonine kinases contains five members (PLK1–5). Most PLKs are involved in cell cycle regulation and DNA damage response. However, PLK5 is different as it lacks a functional kinase domain and is not involved in cell cycle control. PLK5 remains the least-studied family member, and its role in oncogenesis remains enigmatic. Here, we identified tissues with high PLK5 expression by leveraging the Protein Atlas and GTEx databases with relevant literature and selected ovarian, lung, testis, endometrium, cervix, and fallopian tube tissues as candidates for further investigation. Subsequently, we performed immunohistochemical staining for PLK5 on multiple tissue microarrays followed by Vectra scanning and quantitative inForm analysis. This revealed consistently downregulated PLK5 expression in these cancers compared to normal tissues. To validate and extend our findings, we performed pan-cancer analysis of PLK5 expression using public RNAseq databases (TCGA and GTEx). We found PLK5 is downregulated in 18 cancer types, including our selected candidates. Interestingly, we also observed PLK5 expression remains consistently low in later stages of cancer, suggesting PLK5 may have a greater role in tumor initiation than cancer progression. Overall, our study demonstrates PLK5 downregulation in multiple cancers, highlighting its role as a tumor suppressor.
Current Knowledge about the Peritumoral Microenvironment in Glioblastoma
Authors: Trevisi Gianluca , Mangiola Annunziato
Published: November 2023

Glioblastoma is a deadly disease, with a mean overall survival of less than 2 years from diagnosis. Recurrence after gross total surgical resection and adjuvant chemo-radiotherapy almost invariably occurs within the so-called peritumoral brain zone (PBZ). The aim of this narrative review is to summarize the most relevant findings about the biological characteristics of the PBZ currently available in the medical literature. The PBZ presents several peculiar biological characteristics. The cellular landscape of this area is different from that of healthy brain tissue and is characterized by a mixture of cell types, including tumor cells (seen in about 30% of cases), angiogenesis-related endothelial cells, reactive astrocytes, glioma-associated microglia/macrophages (GAMs) with anti-inflammatory polarization, tumor-infiltrating lymphocytes (TILs) with an “exhausted” phenotype, and glioma-associated stromal cells (GASCs). From a genomic and transcriptomic point of view, compared with the tumor core and healthy brain tissue, the PBZ presents a “half-way” pattern with upregulation of genes related to angiogenesis, the extracellular matrix, and cellular senescence and with stemness features and downregulation in tumor suppressor genes. This review illustrates that the PBZ is a transition zone with a pre-malignant microenvironment that constitutes the base for GBM progression/recurrence. Understanding of the PBZ could be relevant to developing more effective treatments to prevent GBM development and recurrence.
Quantification of Gleason Pattern 4 at MRI-Guided Biopsy to Predict Adverse Pathology at Radical Prostatectomy in Intermediate-Risk Prostate Cancer Patients
Authors: Kamecki Hubert , Mielczarek Łukasz , Szempliński Stanisław , Dębowska Małgorzata , Rajwa Paweł , Baboudjian Michael , Klemm Jakob , Rivas Juan Gómez , Modzelewska Elza , Tayara Omar , Malewski Wojciech , Szostek Przemysław , Poletajew Sławomir , Kryst Piotr , Sosnowski Roman , Nyk Łukasz
Published: November 2023

Background: Data on Gleason pattern 4 (GP4) amount in biopsy tissue is important for prostate cancer (PC) risk assessment. We aim to investigate which GP4 quantification method predicts adverse pathology (AP) at radical prostatectomy (RP) the best in men diagnosed with intermediate-risk (IR) PC at magnetic resonance imaging (MRI)-guided biopsy. Methods: We retrospectively included 123 patients diagnosed with IR PC (prostate-specific antigen <20 ng/mL, grade group (GG) 2 or 3, no iT3 on MRI) at MRI-guided biopsy, who underwent RP. Twelve GP4 amount-related parameters were developed, based on GP4 quantification method (absolute, relative to core, or cancer length) and site (overall, targeted, systematic biopsy, or worst specimen). Additionally, we calculated PV×GP4 (prostate volume × GP4 relative to core length in overall biopsy), aiming to represent the total GP4 volume in the prostate. The associations of GP4 with AP (GG ≥ 4, ≥pT3a, or pN1) were investigated. Results: AP was reported in 39 (31.7%) of patients. GP4 relative to cancer length was not associated with AP. Of the 12 parameters, the highest ROC AUC value was seen for GP4 relative to core length in overall biopsy (0.65). an even higher AUC value was noted for PV × GP4 (0.67), with a negative predictive value of 82.8% at the optimal threshold. Conclusions: The lack of an association of GP4 relative to cancer length with AP, contrasted with the better performance of other parameters, indicates directions for future research on PC risk stratification to accurately identify patients who may not require immediate treatment. Incorporating formulas aimed at GP4 volume assessment may lead to obtaining models with the best discrimination ability.
Computational Multi-Scale Modeling of Drug Delivery into an Anti-Angiogenic Therapy-Treated Tumor
Authors: Mohammadi Mahya , Sefidgar Mostafa , Aghanajafi Cyrus , Kohandel Mohammad , Soltani M.
Published: November 2023

The present study develops a numerical model, which is the most complex one, in comparison to previous research to investigate drug delivery accompanied by the anti-angiogenesis effect. This paper simulates intravascular blood flow and interstitial fluid flow using a dynamic model. The model accounts for the non-Newtonian behavior of blood and incorporates the adaptation of the diameter of a heterogeneous microvascular network derived from modeling the evolution of endothelial cells toward a circular tumor sprouting from two-parent vessels, with and without imposing the inhibitory effect of angiostatin on a modified discrete angiogenesis model. The average solute exposure and its uniformity in solid tumors of different sizes are studied by numerically solving the convection-diffusion equation. Three different methodologies are considered for simulating anti-angiogenesis: modifying the capillary network, updating the transport properties, and considering both microvasculature and transport properties modifications. It is shown that anti-angiogenic therapy decreases drug wash-out in the periphery of the tumor. Results show the decisive role of microvascular structure, particularly its distribution, and interstitial transport properties modifications induced via vascular normalization on the quality of drug delivery, such that it is improved by 39% in uniformity by the second approach in R = 0.2 cm.
Efficient Synthesis of 2-Aminoquinazoline Derivatives via Acid-Mediated [4+2] Annulation of N-Benzyl Cyanamides
Authors: Qin Zhao-Yi , Sun Chen-Xi , Zhang Wen-Wen , Li Jun-Ru , Gong Yin-Xiang , Shu Wen-Ming , Wu An-Xin
Published: November 2023

The synthesis of 2-aminoquinazoline derivatives is achieved by using hydrochloric acid as a mediator in the [4+2] annulation reaction between N-benzyl cyanamides and 2-amino aryl ketones. In addition, 2-amino-4-iminoquinazolines are synthesized by the reaction of 2-aminobenzonitriles, instead of 2-amino aryl ketones, with N-benzyl cyanamides. A wide range of substrates can be used and high yields are obtained, demonstrating the practicality of this method for the synthesis of 2-aminoquinazoline derivatives.
How to Differentiate between Resistant and Susceptible Wheat Cultivars for Leaf Rust Fungi Using Antioxidant Enzymes and Histological and Molecular Studies?
Authors: Omara Reda I. , Alkhateeb Omar Abdullah , Abdou Ahmed Hassan , El-Kot Gabr A. , Shahin Atef A. , Saad-El-Din Heba I. , Abdelghany Rady , AL-Shammari Wasimah B. , Albadrani Muayad , Hafez Yaser , Abdelaal Khaled
Published: November 2023

Eight wheat cultivars, Sakha-94, Giza-171, Sids-1, Sids-12, Sids-13, Shandweel-1, Misr-1, and Misr-2, were evaluated for leaf rust at the seedling and adult stages in the 2021 and 2022 seasons. Biochemical, histological, and genetic analyses were performed to determine the link between cultivars that were either sensitive or resistant to the disease. Misr-2 and Giza-171 cultivars had the highest levels of resistance to leaf rust races in 2021 (LTCGT, STSJT, and TTTST) and 2022 (MBGJT, TTTKS, and TTTTT) at the seedling stage. However, at the adult stage, Sakha-94, Giza-171, Misr-1, and Misr-2 cultivars had the highest levels of resistance; consequently, they had the lowest final disease severity and the lowest values of AUDPC. The correlation between the seedling reaction and adult reaction was non-significant, with values of 0.4401 and 0.4793 in the 2021 and 2022 seasons, respectively. Throughout the biochemical, histological, and genetic analyses, it was observed that catalase, peroxidase, and polyphenol oxidase activities significantly increased in the resistant cultivars. The discoloration of superoxide (O2-) and hydrogen peroxide (H2O2) significantly decreased in resistant and moderately resistant wheat cultivars (Sakha-94, Giza-171, Misr-1, and Misr-2); higher hydrogen peroxide (H2O2) and superoxide (O2-) levels were recorded for the susceptible cultivars compared to the resistant cultivars. Molecular markers proved that the Lr50 gene was detected in the resistant cultivars. Puccinia triticina infections negatively affected most histological characteristics of flag leaves, especially in susceptible cultivars. The thickness of the blade (µ), the thickness of the upper and lower epidermis (UE and LE), the thickness of mesophyll tissue (MT), and bundle length and width in the midrib were decreased in susceptible cultivars such as Sids-1, Sids-13, and Shandwel-1 compared with resistant cultivars.