bluuebunny/crossref_metadata_2025 huggingface dataset:
Mimicking the immunosuppressive impact of fibroblasts in a 3D multicellular spheroid model
Authors: Grotz Melanie , van Gijzel Lieke , Bitsch Peter , Carrara Stefania C. , Kolmar Harald , Garg Sakshi
Published: July 2024

Targeting the tumor microenvironment (TME) is an attractive strategy for cancer therapy, as tumor cells in vivo are surrounded by many different influential cell types, with complex interactions strongly affecting tumor progression and therapeutic outcome. Cancer-associated fibroblasts (CAFs) represent an abundant stromal cell type in the TME that modulate tumor development by exerting an immunosuppressive effect to influence effector immune cell activation. One promising target for TME-directed therapy is the CAF marker fibroblast activation protein-α (FAP). In this study, we employ a multicellular three-dimensional (3D) spheroid model, including tumor cells, fibroblast cells, and naïve T cells and could observe a protective effect of fibroblasts on tumor cells. Subsequently, we demonstrate that fibroblasts express FAP at differing expression levels in two-dimensional (2D) versus 3D cells. Lastly, we show that in a triple-culture of tumor cells, T cells and fibroblasts, the simultaneous assembly of fibroblasts using the high-affinity ligand oncoFAP with an engineered α-CD3-scFv-Fc-dextran-oncoFAP construct resulted in effective T cell activation to augment immunogenicity. Overall, this model can be routinely used for preclinical screening to study the effects of fibroblasts on the TME in vitro.
Instructor enthusiasm in online lectures: how vocal enthusiasm impacts student engagement, learning, and memory
Authors: Marty-Dugas Jeremy , Rajasingham Maya , McHardy Robert J. , Kim Joe , Smilek Daniel
Published: July 2024

Across two studies we investigated the impact of instructor enthusiasm on student attentional engagement during an online undergraduate lecture, as well as their memory for lecture content and their motivation to watch additional lecture videos on the same topic (Study 2 only). In both studies participants were randomly assigned to watch a 22-min lecture, delivered with either high or low vocal enthusiasm by the instructor. Subjective ratings of instructor enthusiasm/energy confirmed that in both studies the manipulation of instructor enthusiasm was effective. More importantly, in both studies we found that students in the high enthusiasm condition were consistently more engaged over the course of the lecture compared to those in the low enthusiasm condition, and that overall, reports of engagement increased together with ratings of instructor enthusiasm. However, we found no evidence that instructor enthusiasm influenced quiz performance in either study. Nevertheless, Study 2 showed that those in the high enthusiasm condition were more motivated to watch the next lecture than those in the low enthusiasm condition. These findings make an important contribution to the study of online learning and indicate that instructor enthusiasm may be a viable strategy to increase student engagement and motivation in online courses.
Future skills for Industry 4.0 integration and innovative learning for continuing engineering education
Authors: Azofeifa Jose Daniel , Rueda-Castro Valentina , Camacho-Zuñiga Claudia , Chans Guillermo M. , Membrillo-Hernández Jorge , Caratozzolo Patricia
Published: July 2024

Introduction

This research explores leveraging Industry 4.0 technologies and best practices to address the challenges faced by Continuing Engineering Education (CEE) in Higher Education, ensuring its sustainability and relevance. CEE is essential for engineers' continuous professional growth and adaptability, especially in an era marked by swift technological progress and changing job requirements. CEE must adapt to rapid technological advancements and evolving workforce demands. Nevertheless, traditional pedagogical methods often lag behind the needs of modern engineering professionals.

Methods

Through a case study, this study aims to show how skills visualization allows the creation of comparisons between professional scenarios to enhance the effectiveness and efficiency of CEE programs. To achieve this goal, we utilized a platform based on the KSA taxonomy, which enables the visualization of skills and supports creating personalized and adaptive learning.

Results

Our results demonstrate the transformative potential of integrating new technologies and learning approaches in CEE programs. By leveraging Industry 4.0 technologies, developing personalized learning experiences, and embracing Education 4.0 principles, CEE programs can empower the workforce of the future to thrive in an increasingly complex and dynamic landscape.

Discussions

This study underscores the significance of Education 4.0 principles in shaping the future of CEE programs, emphasizing the crucial role of innovative learning approaches and technological integration in empowering the future engineering workforce in the Industry 4.0 era.
Skeletal dysmorphology and mineralization defects in Fgf20 KO mice
Authors: Dlugosova Sylvie , Spoutil Frantisek , Madureira Trufen Carlos Eduardo , Melike Ogan Betul , Prochazkova Michaela , Fedosieieva Olha , Nickl Petr , Aranaz Novaliches Goretti , Sedlacek Radislav , Prochazka Jan
Published: July 2024

Introduction

Fibroblast growth factor 20 (Fgf20), a member of the Fgf9 subfamily, was identified as an important regulator of bone differentiation and homeostasis processes. However, the role of Fgf20 in bone physiology has not been approached yet. Here we present a comprehensive bone phenotype analysis of mice with functional ablation of Fgf20.

Methods

The study conducts an extensive analysis of Fgf20 knockout mice compared to controls, incorporating microCT scanning, volumetric analysis, Fgf9 subfamily expression and stimulation experiment and histological evaluation.

Results

The bone phenotype could be detected especially in the area of​ the lumbar and caudal part of the spine and in fingers. Regarding the spine, Fgf20-/- mice exhibited adhesions of the transverse process of the sixth lumbar vertebra to the pelvis as well as malformations in the distal part of their tails. Preaxial polydactyly and polysyndactyly in varying degrees of severity were also detected. High resolution microCT analysis of distal femurs and the fourth lumbar vertebra showed significant differences in structure and mineralization in both cortical and trabecular bone. These findings were histologically validated and may be associated with the expression of Fgf20 in chondrocytes and their progenitors. Moreover, histological sections demonstrated increased bone tissue formation, disruption of Fgf20-/- femur cartilage, and cellular-level alterations, particularly in osteoclasts. We also observed molar dysmorphology, including root taurodontism, and described variations in mineralization and dentin thickness.

Discussion

Our analysis provides evidence that Fgf20, together with other members of the Fgf9 subfamily, plays a crucial regulatory role in skeletal development and bone homeostasis.
Translating thyroid hormone into clinical practice: lessons learned from the post-hoc analysis on data available from the ThyRepair study
Authors: Pantos Constantinos I. , Grigoriou Konstantinos P. , Trikas Athanasios G. , Alexopoulos Nikolaos A. , Mourouzis Iordanis S.
Published: July 2024

Background

Thyroid hormone (TH) appears to have a reparative action on the postinfarcted myocardium. This novel action was recently tested in a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair). The present study performed a post-hoc analysis of data from the ThyRepair study to provide further insights into the novel actions of TH on the human postischemic myocardium.

Methods

Data from 41 patients participating in the ThyRepair study (n = 20 placebo and n = 21 LT3) were included in the analysis. LT3 treatment started after stenting and continued intravenously for 48 h. All patients had cardiac magnetic resonance (CMR) at hospital discharge; left ventricular (LV) ejection fraction (LVEF%), LV end-diastolic volume index (LVEDVi; mL/m2), LV end-systolic volume index (LVESVi; mL/m2), infarct volume (IV), left ventricular mass index (LVMi) as edema index, and microvascular obstruction (MVO) were assessed. Patients were divided into two groups based on the median value of the IV: patients with IV ≤ 20% of the LV (group A) and patients with IV > 20% (group B). CMR measurements at discharge are expressed as mean ± SD.

Results

In group A, the placebo and T3-treated groups had similar LVEF% (56.8 ± 10.2 vs. 52.2 ± 10.5), LVEDVi (90.9 ± 19.8 vs. 92.8 ± 14.5), and LVESVi (40.8 ± 18.2 vs. 44.9 ± 14.1) at discharge. In group B, LVEDVi and LVESVi were 112 ± 23.8 and 68.3 ± 21.5 for placebo vs. 91.8 ± 18.6 and 49.0 ± 14.0 for the T3-treated group, respectively, p < 0.05. LVEF% was significantly increased in the T3-treated group vs. placebo, 47.3 ± 6.5 vs. 39.9 ± 8.7, p < 0.05. In group B, CMR LVMi was lower in T3-treated patients vs. placebo but did not reach statistical significance (p = 0.1). MVO was 1.95 ± 2.2 in placebo vs. 0.84 ± 0.9 in the LT3-treated group, p = 0.15.

Conclusion

The present study suggests that acute LT3 treatment may exert more favorable effects on the recovery of cardiac function in patients with large infarct size. Furthermore, it signals a potential effect of LT3 on myocardial edema and microvascular obstruction. These novel findings merit further investigation in large trials.
AsmMix: an efficient haplotype-resolved hybrid de novo genome assembling pipeline
Authors: Liu Chao , Wu Pei , Wu Xue , Zhao Xia , Chen Fang , Cheng Xiaofang , Zhu Hongmei , Wang Ou , Xu Mengyang
Published: July 2024

Accurate haplotyping facilitates distinguishing allele-specific expression, identifying cis-regulatory elements, and characterizing genomic variations, which enables more precise investigations into the relationship between genotype and phenotype. Recent advances in third-generation single-molecule long read and synthetic co-barcoded read sequencing techniques have harnessed long-range information to simplify the assembly graph and improve assembly genomic sequence. However, it remains methodologically challenging to reconstruct the complete haplotypes due to high sequencing error rates of long reads and limited capturing efficiency of co-barcoded reads. We here present a pipeline, AsmMix, for generating both contiguous and accurate diploid genomes. It first assembles co-barcoded reads to generate accurate haplotype-resolved assemblies that may contain many gaps, while the long-read assembly is contiguous but susceptible to errors. Then two assembly sets are integrated into haplotype-resolved assemblies with reduced misassembles. Through extensive evaluation on multiple synthetic datasets, AsmMix consistently demonstrates high precision and recall rates for haplotyping across diverse sequencing platforms, coverage depths, read lengths, and read accuracies, significantly outperforming other existing tools in the field. Furthermore, we validate the effectiveness of our pipeline using a human whole genome dataset (HG002), and produce highly contiguous, accurate, and haplotype-resolved assemblies. These assemblies are evaluated using the GIAB benchmarks, confirming the accuracy of variant calling. Our results demonstrate that AsmMix offers a straightforward yet highly efficient approach that effectively leverages both long reads and co-barcoded reads for haplotype-resolved assembly.
Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment
Authors: Yang Xiu , Zhang Zheng-Chao , Lu Yun-Nan , Chen Han-Lin , Wang Hong-Shen , Lin Tao , Chen Qing-Quan , Chen Jin-Shui , He Wu-Bing
Published: July 2024

Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP.

Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses.

Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers.

Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.
Management of triple-negative breast cancer by natural compounds through different mechanistic pathways
Authors: Kaleem Mohammed , Thool Mandar , Dumore Nitin G. , Abdulrahman Abdulrasheed O. , Ahmad Wasim , Almostadi Amal , Alhashmi Mohammad Hassan , Kamal Mohammad Amjad , Tabrez Shams
Published: July 2024

Triple-negative breast cancer (TNBC) is the most severe form of breast cancer, characterized by the loss of estrogen, progesterone, and human epidermal growth factor receptors. It is caused by various genetic and epigenetic factors, resulting in poor prognosis. Epigenetic changes, such as DNA methylation and histone modification, are the leading mechanisms responsible for TNBC progression and metastasis. This review comprehensively covers the various subtypes of TNBC and their epigenetic causes. In addition, the genetic association of TNBC with all significant genes and signaling pathways linked to the progression of this form of cancer has been enlisted. Furthermore, the possible uses of natural compounds through different mechanistic pathways have also been discussed in detail for the successful management of TNBC.
Genome-wide identification of Glycyrrhiza uralensis Fisch. MAPK gene family and expression analysis under salt stress relieved by Bacillus subtilis
Authors: Gao Pengchao , Xiao Jiancai , Guo Wanying , Fan Rui , Zhang Yan , Nan Tiegui
Published: July 2024

Introduction: Research on Glycyrrhiza uralensis, a nonhalophyte that thrives in saline–alkaline soil and a traditional Chinese medicinal component, is focused on improving its ability to tolerate salt stress to increase its productivity and preserve its “Dao-di” characteristics. Furthermore, the inoculation of bioagents such as Bacillus subtilis to increase plant responses to abiotic stressors is currently a mainstream strategy. Mitogen-activated protein kinase (MAPK), a highly conserved protein kinase, plays a significant role in plant responses to various abiotic stress pathways.

Methods: This investigation involved the identification of 21 members of the GuMAPK family from the genome of G. uralensis, with an analysis of their protein conserved domains, gene structures, evolutionary relationships, and phosphorylation sites using bioinformatics tools.

Results: Systematic evolutionary analysis of the 21 GuMAPKs classified them into four distinct subgroups, revealing significant differences in gene structure and exon numbers. Collinearity analysis highlighted the crucial role of segmental duplication in expanding the GuMAPK gene family, which is particularly evident in G. uralensis and shows a close phylogenetic relationship with Arabidopsis thaliana, tomato, and cucumber. Additionally, the identification of phosphorylation sites suggests a strong correlation between GuMAPK and various physiological processes, including hormonal responses, stress resistance, and growth and development. Protein interaction analysis further supported the role of GuMAPK proteins in regulating essential downstream genes. Through examination of transcriptome expression patterns, GuMAPK16-2 emerged as a prospective pivotal regulatory factor in the context of salt stress and B. subtilis inoculation, a finding supported by its subcellular localization within the nucleus.

Discussion: These discoveries offer compelling evidence for the involvement of GuMAPK in the salt stress response and for the exploration of the mechanisms underlying B. subtilis’ enhancement of salt tolerance in G. uralensis.
CD177 is a novel IgG Fc receptor and CD177 genetic variants affect IgG-mediated function
Authors: Li Yunfang , Wu Jianming
Published: July 2024

CD177 plays an important role in the proliferation and differentiation of myeloid lineage cells including neutrophils, myelocytes, promyelocytes, megakaryocytes, and early erythroblasts in bone marrow. CD177 deficiency is a common phenotype in humans. Our previous studies revealed genetic mechanisms of human CD177 deficiency and expression variations. Up to now, immune functions of CD177 remain undefined. In the current study, we revealed human IgG as a ligand for CD177 by using flow cytometry, bead-rosette formation, and surface plasmon resonance (SPR) assays. In addition, we show that CD177 variants affect the binding capacity of CD177 for human IgG. Furthermore, we show that the CD177 genetic variants significantly affect antibody-dependent cell-mediated cytotoxicity (ADCC) function. The demonstration of CD177 as a functional IgG Fc-receptor may provide new insights into CD177 immune function and genetic mechanism underlying CD177 as biomarkers for human diseases.
Nanoparticles loaded with IL-2 and TGF-β promote transplantation tolerance to alloantigen
Authors: Horwitz David A. , Wang Ju Hua , Kim Dongin , Kang Chang , Brion Katja , Bickerton Sean , La Cava Antonio
Published: July 2024

We have previously reported that nanoparticles (NPs) loaded with IL-2 and TGF-β and targeted to T cells induced polyclonal T regulatory cells (Tregs) that protected mice from graft-versus-host disease (GvHD). Here, we evaluated whether administration of these NPs during alloantigen immunization could prevent allograft rejection by converting immunogenic responses to tolerogenic ones. Using C57BL/6 mice and BALB/c mice as either donors or recipients of allogeneic splenocytes, we found that treatment with the tolerogenic NPs in both strains of mice resulted in a marked inhibition of mixed lymphocyte reaction (MLR) to donor cell alloantigen but not to third-party control mouse cells after transfer of the allogeneic cells. The decreased alloreactivity associated with a four- to fivefold increase in the number of CD4+ and CD8+ T regulatory cells (Tregs) and the acquisition of a tolerogenic phenotype by recipient dendritic cells (DCs) in NP-treated mice. As allogeneic cells persisted in NP-treated mice, these findings suggest that tolerogenic NPs can induce alloantigen-specific Tregs and tolerogenic DCs promoting tolerogenic responses to alloantigen. By inhibiting reactivity to allotransplant, this approach could help reduce the need for immune suppression for the maintenance of allografts.
Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis
Authors: Garcinuño Sara , Lalueza Antonio , Gil-Etayo Francisco Javier , Díaz-Simón Raquel , Lizasoain Ignacio , Moraga Ana , Diaz-Benito Blanca , Naranjo Laura , Cabrera-Marante Oscar , Pleguezuelo Daniel Enrique , Ruiz-Ruigomez Maria , Ayuso Blanca , Arrieta Estibaliz , Folgueira Dolores , Paz-Artal Estela , Cueto Cecilia , Lumbreras Carlos , Serrano Antonio , Serrano Manuel
Published: July 2024

Introduction

Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression.

Methods

We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission.

Results

Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71).

Discussion

Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.
Prediction of TERT mutation status in gliomas using conventional MRI radiogenomic features
Authors: Tang Chuyun , Chen Ling , Xu Yifan , Huang Lixuan , Zeng Zisan
Published: July 2024

Objective

Telomerase reverse transcriptase (TERT) promoter mutation status in gliomas is a key determinant of treatment strategy and prognosis. This study aimed to analyze the radiogenomic features and construct radiogenomic models utilizing medical imaging techniques to predict the TERT promoter mutation status in gliomas.

Methods

This was a retrospective study of 304 patients with gliomas. T1-weighted contrast-enhanced, apparent diffusion coefficient, and diffusion-weighted imaging MRI sequences were used for radiomic feature extraction. A total of 3,948 features were extracted from MRI images using the FAE software. These included 14 shape features, 18 histogram features, 24 gray level run length matrix, 14 gray level dependence matrix, 16 gray level run length matrix, 16 gray level size zone matrix (GLSZM), 5 neighboring gray tone difference matrix, and 744 wavelet transforms. The dataset was randomly divided into training and testing sets in a ratio of 7:3. Three feature selection methods and six classification algorithms were used to model the selected features. Predictive performance was evaluated using receiver operating characteristic curve analysis.

Results

Among the evaluated classification algorithms, the combination model of recursive feature elimination (RFE) with linear regression (LR) using six features showed the best diagnostic performance (area under the curve: 0.733, 0.562, and 0.633 in the training, validation, and testing sets, respectively). The next best-performing models were naive Bayes, linear discriminant analysis, autoencoder, and support vector machine. Regarding the three feature selection algorithms, RFE showed the most consistent performance, followed by relief and ANOVA. T1-enhanced entropy and GLSZM derived from T1-enhanced images were identified as the most critical radiomics features for distinguishing TERT promoter mutation status.

Conclusion

The LR and LRLasso models, mainly based on T1-enhanced entropy and GLSZM, showed good predictive ability for TERT promoter mutations in gliomas using radiomics models.
Local variation in brain temperature explains gender-specificity of working memory performance
Authors: Rogala Jacek , Dreszer Joanna , Sińczuk Marcin , Miciuk Łukasz , Piątkowska-Janko Ewa , Bogorodzki Piotr , Wolak Tomasz , Wróbel Andrzej , Konarzewski Marek
Published: July 2024

Introduction

Exploring gender differences in cognitive abilities offers vital insights into human brain functioning.

Methods

Our study utilized advanced techniques like magnetic resonance thermometry, standard working memory n-back tasks, and functional MRI to investigate if gender-based variations in brain temperature correlate with distinct neuronal responses and working memory capabilities.

Results

We observed a significant decrease in average brain temperature in males during working memory tasks, a phenomenon not seen in females. Although changes in female brain temperature were significantly lower than in males, we found an inverse relationship between the absolute temperature change (ATC) and cognitive performance, alongside a correlation with blood oxygen level dependent (BOLD) signal change induced by neural activity. This suggests that in females, ATC is a crucial determinant for the link between cognitive performance and BOLD responses, a linkage not evident in males. However, we also observed additional female specific BOLD responses aligned with comparable task performance to that of males.

Discussion

Our results suggest that females compensate for their brain’s heightened temperature sensitivity by activating additional neuronal networks to support working memory. This study not only underscores the complexity of gender differences in cognitive processing but also opens new avenues for understanding how temperature fluctuations influence brain functionality.
Limitations associated with transcranial direct current stimulation for enhancement: considerations of performance tradeoffs in active-duty Soldiers
Authors: Duffy Michelle J. , Feltman Kathryn A. , Kelley Amanda M. , Mackie Ryan
Published: July 2024

Introduction

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method, popular due to its low cost, ease-of-application, and portability. As such, it has gained traction in examining its potential for cognitive enhancement in a diverse range of populations, including active-duty military. However, current literature presents mixed results regarding its efficacy and limited evaluations of possible undesirable side-effects (such as degradation to cognitive processes).

Methods

To further examine its potential for enhancing cognition, a double-blind, randomized, sham-controlled, within-subjects design, was used to evaluate both online active-anodal and -cathodal on several cognitive tasks administered. Potential undesirable side effects related to mood, sleepiness, and cognitive performance, were also assessed. Active tDCS was applied for 30 min, using 2 mA, to the left dorsolateral prefrontal cortex with an extracephalic reference placed on the contralateral arm of 27 (14 males) active-duty Soldiers.

Results

We report mixed results. Specifically, we found improvements in sustained attention (active-anodal) for males in reaction time (p = 0.024, ηp2 = 0.16) and for sensitivity index in females (p = 0.013, ηp2 = 0.18). In addition, we found faster reaction time (p = 0.034, ηp2 = 0.15) and increased accuracy (p = 0.029, ηp2 = 0.16) associated with executive function (active-anodal and -cathodal), and worsened working memory performance (active-cathodal; p = 0.008, ηp2 = 0.18). Additionally, we found increased risk-taking with active-anodal (p = 0.001, ηp2 = 0.33).

Discussion

tDCS may hold promise as a method for cognitive enhancement, as evidenced by our findings related to sustained attention and executive function. However, we caution that further study is required to better understand additional parameters and limitations that may explain results, as our study only focused on anode vs. cathode stimulation. Risk-taking was examined secondary to our main interests which warrants further experimental investigation isolating potential tradeoffs that may be associated with tDCS simulation.
Behavioral and histological analyses of the mouse Bassoon p.P3882A mutation corresponding to the human BSN p.P3866A mutation
Authors: Tanaka Daiki , Yaguchi Hiroaki , Yoshizaki Kaichi , Kudo Akihiko , Mori Fumiaki , Nomura Taichi , Pan Jing , Miki Yasuo , Takahashi Hidehisa , Hara Taichi , Wakabayashi Koichi , Yabe Ichiro
Published: July 2024

Tauopathy is known to be a major pathognomonic finding in important neurodegenerative diseases such as progressive supranuclear palsy (PSP) and corticobasal degeneration. However, the mechanism by which tauopathy is triggered remains to be elucidated. We previously identified the point mutation c.11596C > G, p.Pro3866Ala in the Bassoon gene (BSN) in a Japanese family with PSP-like syndrome. We showed that mutated BSN may have been involved in its own insolubilization and tau accumulation. Furthermore, BSN mutations have also been related to various neurological diseases. In order to further investigate the pathophysiology of BSN mutation in detail, it is essential to study it in mouse models. We generated a mouse model with the mouse Bassoon p.P3882A mutation, which corresponds to the human BSN p.P3866A mutation, knock-in (KI) and we performed systematic behavioral and histological analyses. Behavioral analyses revealed impaired working memory in a Y-maze test at 3 months of age and decreased locomotor activity in the home cage at 3 and 12 months of age in KI mice compared to those in wild-type mice. Although no obvious structural abnormalities were observed at 3 months of age, immunohistochemical studies showed elevation of Bsn immunoreactivity in the hippocampus and neuronal loss without tau accumulation in the substantia nigra at 12 months of age in KI mice. Although our mice model did not show progressive cognitive dysfunction and locomotor disorder like PSP-like syndrome, dopaminergic neuronal loss was observed in the substantia nigra in 12-month-old KI mice. It is possible that BSN mutation may result in dopaminergic neuronal loss without locomotor symptoms due to the early disease stage. Thus, further clinical course can induce cognitive dysfunction and locomotor symptoms.
Association between waist circumference and chronic pain: insights from observational study and two-sample Mendelian randomization
Authors: Xu Ting , Jin Fan , Yu Yeting , He Jie , Yang Ren , Lv Tian , Yan Zhangjun
Published: July 2024

Background

Current research offers limited clarity on the correlation between waist circumference and chronic pain prevalence.

Objective

This investigation seeks to elucidate the potential relationship between waist circumference and chronic pain and their causal association.

Methods

An observational study was conducted, leveraging data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2004. The multivariable logistic regression was used to assess the relationship between waist circumference and chronic pain. Furthermore, a meta-analysis of Mendelian Randomization (MR) was applied to explore a causal relationship between waist circumference and pain.

Results

The observational study, post multivariable adjustment, indicated that an increase in waist circumference by 1 dm (decimeter) correlates with a 14% elevation in chronic pain risk (Odds Ratio [OR] = 1.14, 95% Confidence Interval [CI]: 1.04–1.24, p = 0.01). Moreover, the meta-analysis of MR demonstrated that an increased waist circumference was associated with a genetic predisposition to pain risk (OR = 1.14, 95%CI: 1.06–1.23, p = 0.0007).

Conclusion

Observational analysis confirmed a significant relationship between increased waist circumference and the incidence of chronic pain, and results based on MR Study identified increased waist circumference as potentially causal for pain.
Radiomics based on 18F-FDG PET/CT for prediction of pathological complete response to neoadjuvant therapy in non-small cell lung cancer
Authors: Liu Jianjing , Sui Chunxiao , Bian Haiman , Li Yue , Wang Ziyang , Fu Jie , Qi Lisha , Chen Kun , Xu Wengui , Li Xiaofeng
Published: July 2024

Purpose

This study aimed to establish and evaluate the value of integrated models involving 18F-FDG PET/CT-based radiomics and clinicopathological information in the prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) for non-small cell lung cancer (NSCLC).

Methods

A total of 106 eligible NSCLC patients were included in the study. After volume of interest (VOI) segmentation, 2,016 PET-based and 2,016 CT-based radiomic features were extracted. To select an optimal machine learning model, a total of 25 models were constructed based on five sets of machine learning classifiers combined with five sets of predictive feature resources, including PET-based alone radiomics, CT-based alone radiomics, PET/CT-based radiomics, clinicopathological features, and PET/CT-based radiomics integrated with clinicopathological features. Area under the curves (AUCs) of receiver operator characteristic (ROC) curves were used as the main outcome to assess the model performance.

Results

The hybrid PET/CT-derived radiomic model outperformed PET-alone and CT-alone radiomic models in the prediction of pCR to NAT. Moreover, addition of clinicopathological information further enhanced the predictive performance of PET/CT-derived radiomic model. Ultimately, the support vector machine (SVM)-based PET/CT radiomics combined clinicopathological information presented an optimal predictive efficacy with an AUC of 0.925 (95% CI 0.869–0.981) in the training cohort and an AUC of 0.863 (95% CI 0.740–0.985) in the test cohort. The developed nomogram involving radiomics and pathological type was suggested as a convenient tool to enable clinical application.

Conclusions

The 18F-FDG PET/CT-based SVM radiomics integrated with clinicopathological information was an optimal model to non-invasively predict pCR to NAC for NSCLC.
Protein nanoparticles induce the activation of voltage-dependent non-selective ion channels to modulate biological osmotic pressure in cytotoxic cerebral edema
Authors: Fan Wei , Liu Liming , Yin Yuxuan , Zhang Jiayi , Qiu Zhaoshun , Guo Jun , Li Guangming
Published: July 2024

Introduction

Cytotoxic cerebral edema is a serious complication associated with cerebral ischemic stroke and is widely treated using the hypertonic dehydrant. Here, we propose, for the first time, the decrease of intracellular osmosis as a treatment strategy for alleviating cytotoxic cerebral edema.

Methods

We established a fluorescence resonance energy transfer-based intermediate filament tension probe for the study and in situ evaluation of osmotic gradients, which were examined in real-time in living cells from primary cultures as well as cell lines. The MCAO rat model was used to confirm our therapy of cerebral edema.

Results

Depolymerization of microfilaments/microtubules and the production of NLRP3 inflammasome resulted in an abundance of protein nanoparticles (PNs) in the glutamate-induced swelling of astrocytes. PNs induced changes in membrane potential and intracellular second messengers, thereby contributing to hyper-osmosis and the resultant astrocyte swelling via the activation of voltage-dependent nonselective ion channels. Therefore, multiple inhibitors of PNs, sodium and chloride ion channels were screened as compound combinations, based on a decrease in cell osmosis and astrocyte swelling, which was followed by further confirmation of the effectiveness of the compound combination against alleviated cerebral edema after ischemia.

Discussion

The present study proposes new pathological mechanisms underlying “electrophysiology-biochemical signal-osmotic tension,” which are responsible for cascade regulation in cerebral edema. It also explores various compound combinations as a potential treatment strategy for cerebral edema, which act by multi-targeting intracellular PNs and voltage-dependent nonselective ion flux to reduce astrocyte osmosis.
Four-year review of safe and effective procedural sedation in neonates and young infants
Authors: Cui Yu , Tang Min , Mu Qixia , Wu Qunying , Kang Lu , Chen Qin , He Yani
Published: July 2024

Objectives

Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population.

Study design

This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups.

Results

Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants.

Conclusion

This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient’s tolerance.
Chinese classical decoction Wuwei Xiaodu Drink alleviates gout arthritis by suppressing NLRP3-Mediated inflammation
Authors: Lin Na , Dai Qiaoding , Zhang Yan , Xu Liping
Published: July 2024

Background: Wuwei Xiaodu Drink (WWXDD), a classical decoction of traditional Chinese medicine, has been clinically used for the treatment of gout in China for many years. This study aimed to demonstrate the efficacy of WWXDD in treating gout flares and elucidate its underlying therapeutic mechanism.

Methods: A randomized control trial was conducted to compare the effectiveness of WWXDD with low-dose colchicine in gout arthritis. The primary outcome was the clinical response rate on the 7th day, and joint syndrome score and serological tests were secondary outcome measures and were compared in the two groups on the 1st and 7th day. Then we used a network pharmacology approach to investigate the possible mechanism of WWXDD in treating gout, and the effects of WWXDD on the MSU-induced rat model were observed.

Results: In the clinical trial, a total of 78 participants completed the study, and the results demonstrated comparable clinical complete response rates, joint symptom scores, and serological test outcomes between the two groups on the 7th day. Network pharmacology analysis identified 51 core genes that target gout and WWXDD interactions. Notably, strong significant correlations were observed with inflammation cytokine genes and metabolism-related genes. Furthermore, it was found that WWXDD reduced gene expression levels of inflammation cytokines including IL-1β, TNF, and IL-18 in an MSU-induced rat model while increasing IL-10 expression. Additionally, WWXDD decreased insulin gene expression in this model. Moreover, WWXDD exhibited a reduction in both gene and protein expressions associated with the NLRP3-mediated inflammatory pathway in inflamed joints of rats.

Conclusion: The results of the present study suggested the anti-inflammatory effects of WWXDD in the treatment of gouty arthritis, partially through inhibiting NLRP3 inflammasome activation.

Clinical Trial Registration:ClinicalTrials.gov, identifier ChiCTR2100047807.
Sex-specific effects of alcohol on neurobehavioral performance and endoplasmic reticulum stress: an analysis using neuron-specific MANF deficient mice
Authors: Wen Wen , Li Hui , Lauffer Marisol , Hu Di , Zhang Zuohui , Lin Hong , Wang Yongchao , Leidinger Mariah , Luo Jia
Published: July 2024

Excessive alcohol exposure can cause neurobehavioral deficits and structural alterations in the brain. Emerging research evidence suggests that endoplasmic reticulum (ER) stress plays an important role in alcohol-induced neurotoxicity. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein and is responsible to maintain ER homeostasis. MANF is highly expressed in both the developing and mature brain. We have previously shown that MANF deficiency exacerbated alcohol induced neurodegeneration and ER stress in the developing brain. However, little is known regarding the role of MANF in alcohol induced neuronal damage in the adult brain. In this study, we used a neuron-specific MANF knockout (KO) mouse model to investigate the effect of MANF deficiency on acute binge alcohol exposure-induced neurobehavioral deficits and ER stress. Adult male and female MANF KO mice and littermate controls received daily alcohol gavage (5 g/kg) for 10 days and then subjected to a battery of neurobehavioral tests including rotarods, balance beam, DigiGait, open field, elevated plus maze, Barnes maze, and three-chamber sociability task. Female MANF KO animals were more susceptible to alcohol-induced body weight loss. Alcohol exposure did not affect motor function, however female but not male MANF KO mice exhibited an increased locomotor activity in open field test. Learning and memory was not significantly impaired, but it was altered by MANF deficiency in females while it was affected by alcohol treatment in males. Both alcohol-exposed male and female MANF KO mice displayed increased sociability. Alcohol induced the expression of ER chaperones GRP78 and GRP94 and altered the levels of several unfolded protein response (UPR) and neuroinflammation markers in MANF KO mice in a sex-specific manner. The expression of MANF interacting proteins neuroplastin, PDIA1, and PDIA6 was increased in MANF KO mice, and was further induced by alcohol. In conclusion, alcohol exposure and neuronal MANF deficiency interacted to alter neurobehavioral outcomes, ER homeostasis and neuroinflammation in a sex-specific manner.
Exploring the gut microbiota’s crucial role in acute pancreatitis and the novel therapeutic potential of derived extracellular vesicles
Authors: Li Yijie , Li Jie , Li Sen , Zhou Shumin , Yang Jiahua , Xu Ke , Chen Yafeng
Published: July 2024

During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.
Predictors of academic engagement of high school students: academic socialization and motivational beliefs
Authors: Woreta Getachew Tassew
Published: July 2024

The potential of academic engagement to enhance academic outcomes and well-being has been empirically supported, yet studies addressing its predictors are too limited. Hence, the current study collected self-report cross-sectional data from randomly selected 614 (male = 323) high school students in Ethiopia and examined the relations of academic socialization (parental and peer), self-efficacy, and outcome expectations in explaining variance in academic engagement, guided by an integrative model of engagement. Structural equation modeling with the maximum likelihood method indicated that (a) the hypothesized model fit the data well, (b) direct paths from parental and peer academic socialization to self-efficacy, outcome expectations, and academic engagement were positive and significant, (c) the relationships of the constructs in the model explained a significant portion of the variance in academic engagement, and (d) self-efficacy and outcome expectations significantly and positively but partially mediated the pathway from academic socialization to academic engagement. The findings’ implications for boosting student academic engagement were forwarded.
One Health education for criticality on vaccination in teacher training
Authors: Martínez-Pena Inés , Puig Blanca , Uskola Araitz
Published: July 2024

Introduction

Vaccines are the basis of health of our communities since they prevent severe infectious diseases. However vaccination rates continue to decrease due to the spread of misinformation about their side effects, which enhances vaccine hesitancy and puts at risk public health. Introducing vaccines from the One Health approach can help to develop an integral understanding of their role and to apply critical ignorance as part of criticality to avoid vaccine hesitancy and raise trust in science. This paper presents a design on vaccination for secondary-education teacher training developed toward this goal.

Methods

The design presented in this paper draws from previous studies on critical thinking, on vaccine rejection, and the One Health approach on other health issues in Secondary Education. The focus of this design is engaging secondary-education pre-service teachers in the practice of critical ignorance and criticality to assess diverse pieces of information on vaccination from the One Health approach.

Results

This study discusses the design principles and the activities of an original design that aims to provide Secondary Education teachers with some tools to introduce critical ignorance and criticality for addressing misinformation on vaccines by using the One Health approach.

Discussion

If secondary science teachers are going to successfully confront misinformation on vaccination in their science instruction, we need to develop and test designs and approaches that prepare them for this purpose. Critical ignorance plays a central role in managing misinformation; thus, such instruction should engage future teachers in critical evaluation of information on vaccination, as well as in the application of the One Health approach to take responsible actions.