bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and factor structure of the teaching approach scale
Authors: Reho Matteo , Costa Sara , Pirchio Sabine , Limone Pierpaolo , Fuccio Raffaele Di , Gennaro Alessandro
Published: August 2024

Introduction

The study presents the development and validation of the Teaching Approach Scale (TAS), a tool aimed at assessing teaching approaches in educational settings. Literature emphasizes the significance of collaboration and a student-centered approach in enhancing learning environments. However, the translation of these approaches into daily practices faces challenges due to entrenched traditions and individual perspectives. The TAS addresses this gap by assessing educators’ perspectives on teaching approaches.

Method

Exploratory and confirmatory factor analyses carried on a sample of 642 teachers revealed four dimensions defining learning approaches: (a) Development of students’ autonomy, (b) Comparison and synergy in the teacher’s group, (c) Development of the student as a person, and (d) Standardization of teaching.

Results and discussion

The TAS serves as a valuable instrument for capturing teachers’ perspectives on teaching, thereby offering valuable insights for enhancing teaching practices and fostering professional development. Further studies need to face TAS validity and reliability, nevertheless, this study underscores the importance of considering teacher learning cultures in improving educational procedures, highlighting the role of individual perspectives in shaping teaching practices and learning environments.
Family and higher education: developing a comprehensive framework of parents’ support and expectations of first-generation students
Authors: Flanagan-Bórquez Andrea , Soriano-Soriano Gabriel
Published: August 2024

Postsecondary institutions must help all students develop knowledge and skills to persist. Traditional approaches to first-generation students (FGS) have focused on describing the hindrances they experience during their undergraduate trajectories, defying their persistence. This qualitative study explores the experiences of FGS parents; specifically, the characteristics of their support and expectations toward FGS. Semi-structured individual interviews were conducted with 25 FGS parents from diverse Chilean universities. The data collected were analyzed through an inductive process, which included describing, classifying, and interpreting data into categories and themes. The results show that the motivation of families lies in the symbolism that they ascribe to higher education, deploying various modes of family support and resources to ensure that students complete their studies and attain a degree. This process is tailored to meet the initial expectations of FGS performance at university, which typically frame the type of support the family may provide. Postsecondary institutions and policymakers can use this study to develop future policies and practices that include FGS parents’ perspective, expectations and characteristics of support, articulating these with academic culture, FGS’s trajectories and own expectations to reduce inequality and promote retention.
Surgical management of papillary thyroid carcinoma coexisting with Hashimoto’s disease: a single-center retrospective cohort study
Authors: Zhang Dongdong , Wu Jixiang , Chen Lin
Published: August 2024

Background

The mechanism and impact of Hashimoto’s disease (HT) in patients with papillary thyroid carcinoma (PTC) remains a subject of ongoing debate. The optimal extent of thyroid resection is also controversial in cases of low-risk PTC.

Objective

To investigate the clinical outcomes and prognoses associated with different extents of surgical resection in patients diagnosed with PTC coexisting with HT.

Methods

We retrospectively analyzed data on the clinical features and treatment outcomes of patients with PTC concomitant with HT who underwent lobectomy with isthmusectomy and those who underwent total thyroidectomy at Peking University International Hospital between December 2014 and August 2023.

Results

Twenty-one patients in group A underwent lobectomy with isthmusectomy and prophylactic central neck dissection, whereas twenty patients in group B underwent total thyroidectomy with prophylactic central lymph node (LN) dissection, except one who did not undergo LN dissection. Group A demonstrated shorter surgery time (105.75 min ± 29.35 vs. 158.81 min ± 42.01, p = 0.000), higher parathyroid hormone (PTH) levels on postoperative day 1 [26.96 pg/ml (20.25, 35.45) vs. 9.01 pg/ml (2.48, 10.93), p = 0.000] and a shorter postoperative hospital stay [2.95 d (2.0, 4.0) vs. 4.02 d (3.0, 5.0), p = 0.008] than those of group B, with statistically significant differences. Both groups exhibited similar recovery patterns in terms of PTH [32.10 pg/ml (22.05, 46.50) vs. 20.47 pg/ml (9.43, 34.03), p = 0.192] and serum calcium (2.37 mmol/L ± 0.06 vs. 2.29 mmol/L ± 0.19, p = 0.409) after 1 montsh following the surgery. According to the Kaplan-Meier curves, no significant difference in the 5-year disease-free survival rates were observed between patients in group A (100%) and group B (97.1%) (Log rank test: p = 0.420, Breslow test: p = 0.420).

Conclusion

Lobectomy with isthmusectomy and prophylactic central neck dissection is a safe and feasible treatment option for patients with low-risk PTC coexisting with HT.

Clinical trial registration

http://www.chictr.org.cn, identifier ChiCTR2300079115.
Antagonistic interactions between maize seeds microbiome species and the late wilt disease agent, Magnaporthiopsis maydis
Authors: Degani Ofir , Ayoub Aseel , Dimant Elhanan , Gordani Asaf
Published: August 2024

Magnaporthiopsis maydis is a maize pathogen that causes severe damage to commercial corn fields in the late growth stages. Late wilt disease (LWD) has spread since its discovery in the 1960s in Egypt and is now reported in about 10 countries. The pathogen has a hidden endophytic lifecycle in resistant corn plants and secondary hosts such as green foxtail, watermelon lupin and cotton. At the same time, it could be an opportunist and hinder the host development under the right conditions. This study uncovered M. maydis interactions with newly identified maize endophytes. To this end, six fungi were isolated from the seeds of three sweet corn cultivars having varying susceptibility to LWD. These isolates were identified using colony morphology and microscopic characterization, universal internal transcribed spacer (ITS) molecular targeting and phylogenetic analysis. Most of them belonged to pathogenic species. Compared to three previously identified bioprotective microorganisms, the new species were tested for their ability to secrete metabolites that repress M. maydis in vitro and to antagonize it in a solid media confront test and a seedlings pathogenicity assay. The opportunistic fungal species Aspergillus flavus (ME1), Aspergillus terreus (PE3) and the reference biocontrol bacteria Bacillus subtilis (R2) achieved the highest M. maydis inhibition degree in the plates tests (74-100% inhibition). The seedlings’ pathogenicity assay that predicts the seeds’ microflora resistance to M. maydis highlighted the bio-shielding potential of most species (23% or more epicotyl elongation over the infected control). Fusarium sp. (ME2) was the leading species in this measure (43% enhancement), and B. subtilis gave the best protection in terms of seeds’ germination (50%) and sprouts’ biomass (34%). The results of this study could enhance our understanding of the pathobiome’s role in the context of LWD and represent a first step in using the seeds’ natural protective microflora to develop novel management strategies.
Gut resistome of NSCLC patients treated with immunotherapy
Authors: Iwan Ewelina , Grenda Anna , Bomba Arkadiusz , Bielińska Katarzyna , Wasyl Dariusz , Kieszko Robert , Rolska-Kopińska Anna , Chmielewska Izabela , Krawczyk Paweł , Rybczyńska-Tkaczyk Kamila , Olejnik Małgorzata , Milanowski Janusz
Published: August 2024

Background

The newest method of treatment for patients with NSCLC (non-small cell lung cancer) is immunotherapy directed at the immune checkpoints PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1). PD-L1 is the only validated predictor factor for immunotherapy efficacy, but it is imperfect. Some patients do not benefit from immunotherapy and may develop primary or secondary resistance. This study aimed to assess the intestinal resistome composition of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors in the context of clinical features and potentially new prediction factors for assessing immunotherapy efficacy.

Methods

The study included 30 advanced NSCLC patients, 19 (57%) men and 11 (33%) women treated with first- or second-line immunotherapy (nivolumab, pembrolizumab or atezolizumab). We evaluated the patient’s gut resistome composition using the high sensitivity of targeted metagenomics.

Results

Studies have shown that resistome richness is associated with clinical and demographic factors of NSCLC patients treated with immunotherapy. Smoking seems to be associated with an increased abundance of macrolides, lincosamides, streptogramins and vancomycin core resistome. The resistome of patients with progression disease appears to be more abundant and diverse, with significantly higher levels of genomic markers of resistance to lincosamides (lnuC). The resistance genes lnuC, msrD, ermG, aph(6), fosA were correlated with progression-free survival or/and overall survival, thus may be considered as factors potentially impacting the disease.

Conclusion

The results indicate that the intestinal resistome of NSCLC patients with immune checkpoint inhibitors treatment differs depending on the response to immunotherapy, with several distinguished markers. Since it might impact treatment efficacy, it must be examined more deeply.
Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: a Mendelian randomization study
Authors: Su Tao , Peng Xiang , Gan Ying , Wu Hongzhen , Ma Shulin , Zhi Min , Lu Yi , Dai Shixue , Yao Jiayin
Published: August 2024

Background

Iron status has been implicated in gastrointestinal diseases and gut microbiota, however, confounding factors may influence these associations.

Objective

We performed Mendelian randomization (MR) to investigate the associations of iron status, including blood iron content, visceral iron content, and iron deficiency anemia with the incidence of 24 gastrointestinal diseases and alterations in gut microbiota.

Methods

Independent genetic instruments linked with iron status were selected using a genome-wide threshold of p = 5 × 10−6 from corresponding genome-wide association studies. Genetic associations related to gastrointestinal diseases and gut microbiota were derived from the UK Biobank, the FinnGen study, and other consortia.

Results

Genetically predicted higher levels of iron and ferritin were associated with a higher risk of liver cancer. Higher levels of transferrin saturation were linked to a decreased risk of celiac disease, but a higher risk of non-alcoholic fatty liver disease (NAFLD) and liver cancer. Higher spleen iron content was linked to a lower risk of pancreatic cancer. Additionally, higher levels of liver iron content were linked to a higher risk of NAFLD and liver cancer. However, certain associations lost their statistical significance upon accounting for the genetically predicted usage of cigarettes and alcohol. Then, higher levels of iron and ferritin were associated with 11 gut microbiota abundance, respectively. In a secondary analysis, higher iron levels were associated with lower diverticular disease risk and higher ferritin levels with increased liver cancer risk. Higher levels of transferrin saturation were proven to increase the risk of NAFLD, alcoholic liver disease, and liver cancer, but decrease the risk of esophageal cancer. MR analysis showed no mediating relationship among iron status, gut microbiota, and gastrointestinal diseases.

Conclusion

This study provides evidence suggesting potential causal associations of iron status with gastrointestinal diseases and gut microbiota, especially liver disease.
A galactic approach to neutron scattering science
Authors: Watson Gregory R. , Maier Thomas A. , Yakubov Sergey , Doak Peter W.
Published: August 2024

Neutron scattering science is leading to significant advances in our understanding of materials and will be key to solving many of the challenges that society is facing today. Improvements in scientific instruments are actually making it more difficult to analyze and interpret the results of experiments due to the vast increases in the volume and complexity of data being produced and the associated computational requirements for processing that data. New approaches to enable scientists to leverage computational resources are required, and Oak Ridge National Laboratory (ORNL) has been at the forefront of developing these technologies. We recently completed the design and initial implementation of a neutrons data interpretation platform that allows seamless access to the computational resources provided by ORNL. For the first time, we have demonstrated that this platform can be used for advanced data analysis of correlated quantum materials by utilizing the world's most powerful computer system, Frontier. In particular, we have shown the end-to-end execution of the DCA++ code to determine the dynamic magnetic spin susceptibility χ(q, ω) for a single-band Hubbard model with Coulomb repulsion U/t = 8 in units of the nearest-neighbor hopping amplitude t and an electron density of n = 0.65. The following work describes the architecture, design, and implementation of the platform and how we constructed a correlated quantum materials analysis workflow to demonstrate the viability of this system to produce scientific results.
Rare presence and function of neuroendocrine cells in the nasal mucosa
Authors: Wils Tine , Backaert Wout , Jacobs Inge , Ruysseveldt Emma , Cremer Jonathan , Dilissen Ellen , Bullens Dominique M. , Talavera Karel , Steelant Brecht , Van Gerven Laura , Martens Katleen , Hellings Peter W.
Published: August 2024

There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.
In vitro neutralization of IL-6 receptor exacerbates damage to intestinal epithelial cells during Mycobacterium avium paratuberculosis infection
Authors: Alhendi Ala’ , Naser Saleh A.
Published: August 2024

Like TNFα, IL-6 is upregulated in Crohn’s disease (CD) especially in patients associated with Mycobacterium avium paratuberculosis (MAP) infection, and both cytokines have been targeted as a therapeutic option for the treatment of the disease despite the accepted partial response in some patients. Limited response to anti-IL-6 receptor-neutralizing antibodies therapy may be related to the homeostatic dual role of IL-6. In this study, we investigated the effects and the signaling mechanism of IL-6 involved in intestinal epithelial integrity and function during MAP infection using an in vitro model that consists of THP-1, HT-29 and Caco-2 cell lines. Clinically, we determined that plasma samples from MAP-infected CD patients have higher IL-6 levels compared to controls (P-value < 0.001). In CD-like macrophages, MAP infection has significantly upregulated the secretion of IL-6 and the shedding of (IL-6R) from THP-1 macrophages, P-value < 0.05. Intestinal cell lines (Caco-2 and HT-29) were treated with the supernatant of MAP-infected THP-1 macrophages with or without a neutralizing anti-IL-6R antibody. Treating intestinal Caco-2 cells with supernatant of MAP-infected macrophages resulted in significant upregulation of intestinal damage markers including claudin-2 and SERPINE1/PAI-1. Interestingly, blocking IL-6 signaling exacerbated that damage and further increased the levels of the damage markers. In HT-29 cells, MAP infection upregulated MUC2 expression, a protective response that was reversed when IL-6R was neutralized. More importantly, blocking IL-6 signaling during MAP infection rescued damaged Caco-2 cells from MAP-induced apoptosis. The data clearly supports a protective role of IL-6 in intestinal epithelia integrity and function especially in CD patients associated with MAP infection. The findings may explain the ineffective response to anti-IL6 based therapy and strongly support a therapeutic option that restores the physiologic level of IL-6 in patient’s plasma. A new treatment strategy based on attenuation of IL-6 expression and secretion in inflammatory diseases should be considered.
Antigen specificity affects analysis of natural antibodies
Authors: Weston Kendra , Fulton Janet E. , Owen Jeb
Published: August 2024

Natural antibodies are used to compare immune systems across taxa, to study wildlife disease ecology, and as selection markers in livestock breeding. These immunoglobulins are present prior to immune stimulation. They are described as having low antigen specificity or polyreactive binding and are measured by binding to self-antigens or novel exogenous proteins. Most studies use only one or two antigens to measure natural antibodies and ignore potential effects of antigen specificity in analyses. It remains unclear how different antigen-specific natural antibodies are related or how diversity among natural antibodies may affect analyses of these immunoglobulins. Using genetically distinct lines of chickens as a model system, we tested the hypotheses that (1) antigen-specific natural antibodies are independent of each other and (2) antigen specificity affects the comparison of natural antibodies among animals. We used blood cell agglutination and enzyme-linked immunosorbent assays to measure levels of natural antibodies binding to four antigens: (i) rabbit erythrocytes, (ii) keyhole limpet hemocyanin, (iii) phytohemagglutinin, or (iv) ovalbumin. We observed that levels of antigen specific natural antibodies were not correlated. There were significant differences in levels of natural antibodies among lines of chickens, indicating genetic variation for natural antibody production. However, line distinctions were not consistent among antigen specific natural antibodies. These data show that natural antibodies are a pool of relatively distinct immunoglobulins, and that antigen specificity may affect interpretation of natural antibody function and comparative immunology.
A review of psoriasis image analysis based on machine learning
Authors: Li Huihui , Chen Guangjie , Zhang Li , Xu Chunlin , Wen Ju
Published: August 2024

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.
In India, most principal investigators have run very few trials over the years
Authors: Borah Rishima , Samanta Anwesha Dhal , Rajueni Khujith , Vaswani Vina , Saberwal Gayatri
Published: August 2024

Background

In the past, clinical trials run in India have been the subject of criticism. Among other steps to improve the trial ecosystem, for some time the government limited the number of trials that a Principal Investigator (PI) could run to three at a time. We were interested to know how many trials PIs in India tend to run at a time.

Methods

We accessed the 52,149 trial records hosted by the Clinical Trials Registry—India in April 2023. Of these, we shortlisted trials that had run in India, were interventional, and involved certain interventions such as drug, biological etc. We used multiple parameters, such as email ID, phone number etc. to determine whether one name always represented the same PI and whether two names corresponded to the same PI. We then determined how many trials each PI had run.

Results

We found that 3,916 unique PI names were associated with 6,665 trials. Of these, 2,963 (75.7%) PIs had run a single study. Only 251 (6.4%) had run more than three trials. A mere 14 PIs had run 20 or more trials. The 14 PIs were affiliated with local pharma companies (6), local or global contract research organizations (4), multinational pharma companies (3) and the Central Council for Research in Homeopathy (1). The maximum number of trials run by a single PI was 108. Of these, the largest number run in a single year, 2022, was 53.

Conclusion

Each PI name needs to be connected to a unique ID that does not change with time, so that it is easier to track the number of trials that a given PI has run. The number of studies run by a given PI at a given time must not be excessive and needs to be monitored more actively. The government needs to consider whether a cap on the number of trials that a PI runs at a time is required and what infrastructure needs to be in place to facilitate higher numbers of trials. Trial registry records need to be updated more regularly. Other countries may wish to do likewise.
Assessing the efficacy of natural soil biotin on soil quality, microbial diversity, and Rhododendron simsii growth for sustainable landscape architecture
Authors: Teng Zhiyan , Chen Lan , Li Sheng , Pan Kexuan , Liu Dandan , Gu Zaiyuan , Wang Yijie , Huang Li , Chen Yunwen
Published: August 2024

Fertilization significantly influences soil quality and its sustainable use in urban garden maintenance. The widespread application of inorganic fertilizers has raised ecological concerns due to their potential environmental impacts. Organic fertilizers, while beneficial, often have slow effects and are costly. Biofertilizers, with their eco-friendly nature and low carbon footprint, are gaining attention for their multifaceted role in supporting plant growth. Despite the focus on fruit trees, vegetables, and medicinal plants, ornamental plants have been understudied. This study aims to evaluate the efficacy of a novel microbial fertilizer, ‘natural soil biotin’, on Rhododendron plants, specifically the Azalea hybrid ‘Carnation’. The study employed a comparative approach to assess the impact of different fertilization strategies on soil properties, microbial diversity, enzyme activity, plant morphology, and physiological parameters. The application of ‘natural soil biotin’ was compared with the use of inorganic and organic fertilizers. The combined application of ‘natural soil biotin’ was found to effectively enhance soil properties and mitigate the impact of other fertilizers on soil pH. It also improved the relative abundance of beneficial microbial groups such as Proteobacteria, Ascomycota, and Basidiomycota. Furthermore, the mixed application significantly increased the activities of urease and sucrase in Rhododendron plants, which promoted their growth, development, and stress resistance. The results indicate that the mixed application of ‘natural soil biotin’ with inorganic and organic fertilizers not only improved the soil quality but also enhanced the efficiency of fertilizer utilization. This approach led to increased economic and environmental benefits in Rhododendron cultivation. The findings contribute to the foundation for soil improvement and ecological restoration, suggesting that ‘natural soil biotin’ could be a promising alternative or supplement to traditional fertilization methods in sustainable landscape architecture.
Application of valencene and prospects for its production in engineered microorganisms
Authors: Song Yafeng , Liu Huizhong , Quax Wim J. , Zhang Zhiqing , Chen Yiwen , Yang Ping , Cui Yinhua , Shi Qingshan , Xie Xiaobao
Published: August 2024

Valencene, a sesquiterpene with the odor of sweet and fresh citrus, is widely used in the food, beverage, flavor and fragrance industry. Valencene is traditionally obtained from citrus fruits, which possess low concentrations of this compound. In the past decades, the great market demand for valencene has attracted considerable attention from researchers to develop novel microbial cell factories for more efficient and sustainable production modes. This review initially discusses the biosynthesis of valencene in plants, and summarizes the current knowledge of the key enzyme valencene synthase in detail. In particular, we highlight the heterologous production of valencene in different hosts including bacteria, fungi, microalgae and plants, and focus on describing the engineering strategies used to improve valencene production. Finally, we propose potential engineering directions aiming to further increase the production of valencene in microorganisms.
Cortical lobar volume reductions associated with homocysteine-related subcortical brain atrophy and poorer cognition in healthy aging
Authors: Song Hyun , Bharadwaj Pradyumna K. , Raichlen David A. , Habeck Christian G. , Grilli Matthew D. , Huentelman Matthew J. , Hishaw Georg A. , Trouard Theodore P. , Alexander Gene E.
Published: August 2024

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer’s disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging.
Geometric morphometric analysis of the brainstem and cerebellum in Chiari I malformation
Authors: Perera Ishan R. , Zahed Malek , Moriarty Sydney , Simmons Zachary , Rodriguez Maya , Botkin Courtney , Dickson Taylor , Kasper Bradley , Fahmy Kendyl , Millard Jonathan A.
Published: August 2024

Background

Chiari I malformation (CMI) is characterized by inferior descent of the cerebellar tonsils through the foramen magnum and is associated with headache and neck pain. Many morphometric research efforts have aimed to describe CMI anatomy in the midsagittal plane using classical measurement techniques such as linear dimensions and angles. These methods are less frequently applied to parasagittal features and may fall short in quantifying more intricate anatomy with fewer distinct homologous landmarks.

Methods

Landmark-based geometric morphometric techniques were used to asses CMI morphology in five anatomical planes of interest.

Results

Significant shape differences between CMI and age/sex-matched controls were found in the midsagittal (Pseudo-F = 5.4841, p = 0.001) and axial planes through the rostral medulla (Pseudo-F = 7.6319, p = 0.001). In addition to tonsillar descent, CMI principal component 1 (PC1) scores in the midsagittal protocol were associated with marked anterior concavity of the brainstem and generalized verticality of the cerebellum with anterior rotation of its anterior lobe. In the axial medulla/cerebellum protocol, CMI PC1 scores were associated with greater anterior–posterior (A-P) dimension with loss of medial-lateral (M-L) dimension.

Discussion

These results suggest that CMI is associated with greater curvature of the brainstem and spinal cord, which may perturb normal neural activities and disrupt cerebrospinal fluid movements. Previous reports on the A-P diameter of the posterior fossa in CMI have conflicted; our findings of greater A-P cerebellar dimensionality with concomitant loss of width alludes to the possibility that more caudal aspects of the posterior cranial fossa are more bowl-like (homogenous in axial dimensions) and less trough-like or elongated in the M-L direction.
Evaluation of partial resheathing of EmboTrap III using the microcatheter (PREMIER) technique for fibrin-rich hard clots in an in vitro vessel model
Authors: Namitome Satoshi , Nagao Yoichiro , Shigehatake Yuya , Matsuo Junichi , Kawamoto Keisuke , Kuroki Kenji , Hayashi Hirotaka , Nakajima Makoto , Terasaki Tadashi , Ueda Mitsuharu , Shindo Seigo
Published: August 2024

Background and purpose

Despite the ongoing advancements in mechanical thrombectomy for large vessel occlusions causing acute ischemic stroke, successful recanalization is not achieved in all patients. One contributing factor is the presence of fibrin-rich hard clots. We proposed a new technique called the PREMIER technique, which aims to retrieve fibrin-rich clots. This study evaluated the efficacy of the PREMIER technique on fibrin-rich and erythrocyte-rich clots by comparing it with the simple use of EmboTrap III in an in vitro vessel model.

Methods

The PREMIER technique involves partially resheathing a fully deployed EmboTrap III (CERENOVUS, Johnson & Johnson Medical Devices, Irvine, California, USA) using a microcatheter to capture and retrieve a hard clot between the inner channel and outer cages of EmboTrap III. We compared recanalization rate of the PREMIER technique with the simple use of EmboTrap III in an in vitro vessel model, occluding the M1 segment with fibrin-rich hard clots (0% erythrocyte composition) and erythrocyte-rich clots (50% erythrocyte composition).

Results

Among the 40 procedures (10 each for the PREMIER technique and the simple use of EmboTrap III for two different clots) for fibrin-rich clots, the PREMIER technique achieved successful recanalization in all 10 cases, with a significantly higher recanalization rate than the EmboTrap III (100% vs. 50%, p = 0.03). For erythrocyte-rich clots, the recanalization rate was not significantly different in the PREMIER technique compared with the simple use of EmboTrap III (80% vs. 70%, p = 1.00).

Conclusion

The PREMIER technique is a novel technique for acute large-vessel occlusions caused by fibrin-rich hard clots that hinders successful recanalization during mechanical thrombectomy.
Predicting neurodevelopmental outcomes in extremely preterm neonates with low-grade germinal matrix-intraventricular hemorrhage using synthetic MRI
Authors: Zhang Chunxiang , Zhu Zitao , Wang Kaiyu , Wang Linlin , Lu Jiaqi , Lu Lin , Xing Qingna , Wang Xueyuan , Zhang Xiaoan , Zhao Xin
Published: August 2024

Objectives

This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions.

Materials and methods

In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling.

Results

Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1-FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models.

Conclusion

Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1-Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies.
Vagus nerve electroneurogram-based detection of acute kainic acid induced seizures
Authors: Acedo Reina Elena , Germany Morrison Enrique , Dereli Ayse S. , Collard Elise , Raffoul Romain , Nonclercq Antoine , El Tahry Riëm
Published: August 2024

Seizures produce autonomic symptoms, mainly sympathetic but also parasympathetic in origin. Within this context, the vagus nerve is a key player as it carries information from the different organs to the brain and vice versa. Hence, exploiting vagal neural traffic for seizure detection might be a promising tool to improve the efficacy of closed-loop Vagus Nerve Stimulation. This study developed a VENG detection algorithm that effectively detects seizures by emphasizing the loss of spontaneous rhythmicity associated with respiration in acute intrahippocampal Kainic Acid rat model. Among 20 induced seizures in six anesthetized rats, 13 were detected (sensitivity: 65%, accuracy: 92.86%), with a mean VENG-detection delay of 25.3 ± 13.5 s after EEG-based seizure onset. Despite variations in detection parameters, 7 out of 20 seizures exhibited no ictal VENG modifications and remained undetected. Statistical analysis highlighted a significant difference in Delta, Theta and Beta band evolution between detected and undetected seizures, in addition to variations in the magnitude of HR changes. Binomial logistic regression analysis confirmed that an increase in delta and theta band activity was associated with a decreased likelihood of seizure detection. This results suggest the possibility of distinct seizure spreading patterns between the two groups which may results in differential activation of the autonomic central network. Despite notable progress, limitations, particularly the absence of respiration recording, underscore areas for future exploration and refinement in closed-loop stimulation strategies for epilepsy management. This study constitutes the initial phase of a longitudinal investigation, which will subsequently involve reproducing these experiments in awake conditions with spontaneous recurrent seizures.
Circadian disruptions and their role in the development of hypertension
Authors: Crowthers Raymond , Thi Mong Nguyen Trinh , Martinez Diana
Published: August 2024

Circadian fluctuations in physiological setpoints are determined by the suprachiasmatic nucleus (SCN) which exerts control over many target structures within and beyond the hypothalamus via projections. The SCN, or central pacemaker, orchestrates synchrony between the external environment and the internal circadian mechanism. The resulting cycles in hormone levels and autonomic nervous system (ANS) activity provide precise messages to specific organs, adjusting, for example, their sensitivity to approaching hormones or metabolites. The SCN responds to both photic (light) and non-photic input. Circadian patterns are found in both heart rate and blood pressure, which are linked to daily variations in activity and autonomic nervous system activity. Variations in blood pressure are of great interest as several cardiovascular diseases such as stroke, arrhythmias, and hypertension are linked to circadian rhythm dysregulation. The disruption of normal day-night cycles, such as in shift work, social jetlag, or eating outside of normal hours leads to desynchronization of the central and peripheral clocks. This desynchronization leads to disorganization of the cellular processes that are normally driven by the interactions of the SCN and photic input. Here, we review autonomic system function and dysfunction due to regulation and interaction between different cardiorespiratory brain centers and the SCN, as well as social, lifestyle, and external factors that may impact the circadian control of blood pressure.
Topical application of daphnetin hydrogel for traumatic brain injury
Authors: Ma Yuanhao , Liu Yu , Guo Jianqiang , Chen Zhongjun , Zhao Zongren , Zheng Jinyu
Published: August 2024

Background

Traumatic brain injury (TBI) causes neuronal cell damage and dysfunction. According to previous studies, daphnetin (Dap) has a protective effect in neurological injury. However, the in vivo bioavailability of daphnetin is not high. The purpose of this study was to determine whether administering daphnetin directly into the site of injury via a hydrogel drug carrier could improve its therapeutic impact.

Methods

Tripolycerol monostearates / daphnetin (TM/Dap) hydrogels were prepared and characterised using water bath heating, scanning electron microscopy (SEM) and small animal in vivo imaging techniques. The TBI model was established using the Feeney free fall impact method. Using the Morris water maze test, the mNSS neurological deficit rating scale, haematoxylin-eosin staining, and liver and kidney function tests, the therapeutic benefit of TM/Dap and its toxic side effects were assessed. The therapeutic effects of TM/Dap were further investigated using wet and dry gravimetric methods, Evans blue staining, protein immunoblotting, immunofluorescence staining techniques and ELISA.

Results

The efficacy of the TM/Dap hydrogel in gradually releasing daphnetin in the context of traumatic brain damage was shown by both in vitro and in vivo tests. Behavioral experiments showed that the learning and spatial memory abilities of TM/Dap hydrogel treated mice were significantly improved in the water maze experiment. And TM/Dap hydrogel has high biosafety for organisms. The results of the therapeutic mechanism of action showed that TM/Dap hydrogel showed more significant efficacy in reducing the neuroinflammatory response caused by TNF-α, IL-6 and other factors, as well as promoting the recovery of post-traumatic neurological function.

Conclusion

The use of hydrogel as a drug carrier for daphnetin showed more significant efficacy in reducing neuroinflammatory response, protecting nerve tissue and promoting post-traumatic neurological recovery compared with traditional drug delivery methods.
Interleukin-10 contrasts inflammatory synaptopathy and central neurodegenerative damage in multiple sclerosis
Authors: Gilio Luana , Fresegna Diego , Stampanoni Bassi Mario , Musella Alessandra , De Vito Francesca , Balletta Sara , Sanna Krizia , Caioli Silvia , Pavone Luigi , Galifi Giovanni , Simonelli Ilaria , Guadalupi Livia , Vanni Valentina , Buttari Fabio , Dolcetti Ettore , Bruno Antonio , Azzolini Federica , Borrelli Angela , Fantozzi Roberta , Finardi Annamaria , Furlan Roberto , Centonze Diego , Mandolesi Georgia
Published: August 2024

Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients. In a study involving 184 newly diagnosed relapsing–remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures. Additionally, we examined IL-10 impact on synaptic transmission in striatal medium spiny neurons and its role in counteracting inflammatory synaptopathy induced by IL-1β in female C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Our findings revealed a significant positive correlation between IL-10 CSF levels and changes in EDSS (Expanded Disability Status Scale) scores one year after MS diagnosis. Moreover, IL-10 levels in the CSF were positively correlated with volumes of specific subcortical brain structures, such as the nucleus caudate. In both MS patients’ CSF and EAE mice striatum, IL-10 and IL-1β expressions were upregulated, suggesting possible antagonistic effects of these cytokines. Notably, IL-10 exhibited the ability to decrease glutamate transmission, increase GABA transmission in the striatum, and reverse IL-1β-induced abnormal synaptic transmission in EAE. In conclusion, our data suggest that IL-10 exerts direct neuroprotective effects in MS patients by modulating both excitatory and inhibitory transmission and attenuating IL-1β-induced inflammatory synaptopathy. These findings underscore the potential therapeutic significance of IL-10 in mitigating neurodegeneration in MS.
Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models
Authors: Ye Zhongduo , Zheng Yukun , Li Ningning , Zhang Huaibin , Li Qiangqiang , Wang Xiong
Published: August 2024

Objective

This study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) to mitigate the risk of translational discrepancies from animal experiments to clinical applications.

Methods

We conducted a comprehensive literature search up to March 2024 using PubMed, Embase, Web of Science, and Scopus databases. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies. Data analysis was performed using STATA16 software.

Results

A total of 30 studies were included. The results indicated that BMSCs-Exo significantly improved the BBB score in SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited the expression of the pro-inflammatory cytokine TNF-α (SMD = -3.12, 95% CI [−3.57, −2.67]), and promoted the expression of anti-inflammatory cytokines IL-10 (SMD = 2.76, 95% CI [1.88, 3.63]) and TGF-β (SMD = 3.89, 95% CI [3.02, 4.76]). Additionally, BMSCs-Exo significantly reduced apoptosis levels (SMD = −4.52, 95% CI [−5.14, −3.89]), promoted the expression of axonal regeneration markers NeuN cells/field (SMD = 3.54, 95% CI [2.65, 4.42]), NF200 (SMD = 4.88, 95% CI [3.70, 6.05]), and the number of Nissl bodies (SMD = 1.89, 95% CI [1.13, 2.65]), and decreased the expression of astrogliosis marker GFAP (SMD = −5.15, 95% CI [−6.47, −3.82]). The heterogeneity among studies was primarily due to variations in BMSCs-Exo transplantation doses, with efficacy increasing with higher doses.

Conclusion

BMSCs-Exo significantly improved motor function in SCI rats by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, and promoting axonal regeneration. However, the presence of selection, performance, and detection biases in current animal experiments may undermine the quality of evidence in this study.
Soursop leaf extract and fractions protects against L-NAME-induced hypertension and hyperlipidemia
Authors: Nsor Okim Okim , Alabi Babatunde Adebola , Badejo Joseph Ayo , Afolabi Faith , Nku-Ekpang Okot-Asi , Iwalewa Ezekiel Olugbenga
Published: August 2024

Introduction

Despite the high phenolic content of Annona muricata, little is known about its anti-hypertensive and antihyperlipidemic properties. This study evaluated the anti-hypertensive and antihyperlipidemic potential of A. muricata leaf extracts.

Materials and methods

Forty-two male Wistar rats were divided into seven groups of six animals each. N-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension and hyperlipidemia.

Results

Phytochemical screening of Annona muricata leaf extracts (AMLE) revealed the presence of saponins, alkaloids, flavonoids, tannins, coumarins, steroids, terpenoids, and phenols. Comparing the methanol extract with the ethyl acetate fraction, quantification revealed that the methanol extract contained more phenolics, flavonoids, and alkaloids. The AMLE rats significantly reduced triglycerides, total cholesterol, LDL, VLDL, atherogenic index, coronary risk index, and blood pressure. The significant decrease in GSH, catalase, SOD, GST, and oxidative stress markers (MDA, nitrites, and MPO) was reversed by AMLE in a dose-dependent manner. Also, the elevated serum levels of TNF-α and IL-1β in the hypertensive rats were attenuated in the treatment groups.

Discussion

This study suggests the potential ameliorative effects of Annona muricata leaf extracts against L-NAME-induced hypertension in rats. Notably, the study showed the antioxidant and anti-inflammatory properties of A. muricata leaf extracts, which is seen in its ability to attenuate oxidative stress and inflammatory cytokines in L-NAME-induced hypertensive rats. A. muricata extracts also decreased atherogenic risk and improved lipid profiles.