1,194 results
Search Results
2. A Hybrid Nanofiber/Paper Cell Culture Platform for Building a 3D Blood–Brain Barrier Model.
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Huang, Kaixiang, Castiaux, Andre D., Podicheti, Ram, Rusch, Douglas B., Martin, R. Scott, and Baker, Lane A.
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CELL culture , *BLOOD-brain barrier , *PLURIPOTENT stem cells , *TIGHT junctions , *CENTRAL nervous system , *BASAL lamina , *PHENOTYPES - Abstract
The blood–brain barrier (BBB) protects the central nervous system from toxins and pathogens in the blood by regulating permeation of molecules through the barrier interface. In vitro BBB models described to date reproduce some aspects of BBB functionality, but also suffer from incomplete phenotypic expression of brain endothelial traits, difficulty in reproducibility and fabrication, or overall cost. To address these limitations, a 3D BBB model based on a hybrid paper/nanofiber scaffold is described. The cell culture platform utilizes lens paper as a framework to accommodate 3D culture of astrocytes. An electrospun nanofiber layer is coated onto one face of the paper to mimic the basement membrane and support growth of an organized 2D layer of endothelial cells (ECs). Human induced pluripotent stem cell‐derived ECs and astrocytes are co‐cultured to develop a human BBB model. Morphological and spatial organization of model are validated with confocal microscopy. Measurements of transendothelial resistance and permeability demonstrate the BBB model develops a high‐quality barrier and responds to hyperosmolar treatments. RNA‐sequencing shows introduction of astrocytes both regulates EC tight junction proteins and improves endothelial phenotypes related to vasculogenesis. This model shows promise as a model platform for future in vitro studies of the BBB. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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3. Paper-based biosensor based on phenylalnine ammonia lyase hybrid nanoflowers for urinary phenylalanine measurement.
- Author
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Sun, Baoting, Wang, Zichen, Wang, Xiaoyi, Qiu, Mengxia, Zhang, Zhijin, Wang, Ziyuan, Cui, Jiandong, and Jia, Shiru
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BIOSENSORS , *PHENYLALANINE , *PROTEOLYSIS , *URINE , *PHENYLKETONURIA , *CENTRAL nervous system , *AMMONIA - Abstract
The Phenylketonuria (PKU) is an inborn defect of phenylalanine (Phe) metabolism, in which Phe accumulated in the blood causing alterations at the central nervous system. Therefore, the detection of PKU is very important for the early diagnosis of PKU patients. However, existing tests for PKU are time-consuming and require high-resource laboratories. In this study, a novel paper-based biosensor based on phenylalnine ammonia lyase (PAL) hybrid nanoflowers was constructed that provides a semi-quantitative output of the concentration of Phe from urine samples. PAL@Ca 3 (PO 4) 2 hybrid nanoflowers (PAL@NF) were first prepared using PAL and Ca2+. Synthesis conditions of the PAL@NF on the formation of the PAL@NF were optimized. The PAL@NF exhibited 90% activity recovery under optimal condition. Compared with free PAL, the PAL@NF displayed good storage stability and increased tolerance to proteolysis. After five consecutive operating cycles, the PAL@NF still retained 73% of its initial activity, indicating excellent reusability. Furthermore, the paper-based biosensor was able to detect Phe concentration in urine samples, and exhibited good linearity to the Phe concentrations in the range from 60 to 2400 μM and the response time was only about 10 min. Therefore, the paper-based biosensor can be a promising candidate as a biosensor for the detection of PKU. Unlabelled Image • PAL@Ca 3 (PO 4) 2 hybrid nanoflowers were successfully synthesized. • The PAL@Ca 3 (PO 4) 2 hybrid nanoflowers exhibited high activity and stability. • A paper-based biosensor based on the PAL hybrid nanoflowers for urinary Phe measurement was constructed for the first time. • The paper-based biosensor is expected to become a home-test monitoring for PKU. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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4. The prevention of central nervous system relapse in diffuse large B‐cell lymphoma: a British Society for Haematology good practice paper.
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McKay, Pamela, Wilson, Matthew R., Chaganti, Sridhar, Smith, Jeffery, Fox, Christopher P., and Cwynarski, Kate
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DIFFUSE large B-cell lymphomas , *CENTRAL nervous system , *HEMATOLOGY , *LYMPHOMAS , *CONTRAST-enhanced magnetic resonance imaging - Published
- 2020
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5. Singultus, paper-bag ventilation, and hypercapnia.
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Petroianu, Georg A.
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HYPERCAPNIA , *HICCUPS , *VENTILATION , *PHYSICIANS , *CENTRAL nervous system - Abstract
Sir Louis Francis Knuthsen (1869–1957), the physician who painstakingly listed almost all treatments known for obstinate hiccough, ascribes the holding of breath method to Philip Henry Pye-Smith, FRS (1840–1914), consultant at Guy's Hospital in London. In fact, the strategy is much older and was mentioned by greats such as Francis Bacon (1561–1626), Aristoteles (384–322 BC), and Eryximachus (late-fifth century bce). Hypoventilation to reduce central nervous system excitability was used in antiquity as evidenced by Cyriacus' treatment of Artemia, the daughter of Emperor Diocletian (≈ 244–311). She was suffering from (among others) seizures that Cyriacus was apparently controlling by tightening a scarf around her neck, as depicted by Mathias Grünewald (1460–1528) on a wing of the so-called Heller Altar now on display at the Historical Museum, Frankfurt, Germany. In modern times, around 1920, inducing hypercapnia by CO2 inhalation as therapy for hiccups was suggested and tried by a number of anesthetists, such as Americans Russel Firth Sheldon (1885–1960) and Brian Collins Sword (1889–1956) in Boston; Briton Christopher Langton Hewer (1896–1986) at St. Bartholomew's Hospital in London; Austrian Karl Doppler (1887–1947) in Vienna; and the German/Polish Arthur Dzialoszynski (1893–1977) in Berlin. Although various authors assign the scientific primate to any of them, the first mention of carbon dioxide inhalation as treatment of singultus in the scientific literature is of French origin and was made by Paris pharmacist Henri Bocquillon-Limousin (1856–1917) in his 1892 Formulaire des médicaments nouveaux et des médications nouvelles. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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6. Research Paper: Immune Checkpoint Molecules in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System.
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Monabati, Ahmad, Nematollahi, Pardis, Dehghanian, Amirreza, Safaei, Akbar, Sadeghipour, Alireza, Movahedinia, Sajjadeh, and Mokhtari, Maral
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CENTRAL nervous system , *DIFFUSE large B-cell lymphomas , *PROGRAMMED cell death 1 receptors , *PROGRAMMED death-ligand 1 , *HEMATOLOGIC malignancies , *LYMPHOMAS - Abstract
Introduction: Primary Diffuse Large B Cell Lymphoma of CNS (PCNSL) is a rare variant of Diffuse Large B Cell Lymphoma (DLBCL) and presents with an aggressive clinical course and usually resistant to commonly used therapy regimens. Recently, role of immune checkpoint molecules including PD-1 and PD-L1 confirmed in some solid tumors and lymphoma resulting tumor cells escape the immune system and help to survive and to spread. Inhibitors of PD-1 and PD-L1 have shown lasting responses in several solid and some hematological tumors, while limited studies evaluate checkpoint molecules on PCNSL. Method: In this study, we investigated PD-1 and PD-L1 expression by immunostaining on 71 patients with PCNSL and correlation with demographic data, location of the tumor, proliferation rate, cell of origin, and CD8 positive T cell infiltration in tumor microenvironment. Results: 16 from71 showed PD-1 expression, while PD-L1 expression were 42/71. No association was determined between PD-1/PD-L1 expression and gender, cell of origin, and proliferation rate, but a highly significant difference was determined between the infiltration of CD8 positive T cells in two groups of PD-1/PD-L1 positive and negative. Conclusion: This study revealed expression of check point molecules in remarkable number of PCNSL which may open new therapeutic recommendations in this aggressive lymphoma type. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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7. Is blood pTau a reliable indicator of the CSF status? A narrative review.
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Antonioni, Annibale, Raho, Emanuela Maria, and Di Lorenzo, Francesco
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ALZHEIMER'S disease , *LITERATURE reviews , *TAU proteins , *NEUROFIBRILLARY tangles , *CENTRAL nervous system - Abstract
Background: The identification of biomarkers for the early diagnosis of Alzheimer's disease (AD) is a crucial goal of the current research. Blood biomarkers are less invasive, easier to obtain and achievable by a cheaper means than those on cerebrospinal fluid (CSF) and significantly more economic than functional neuroimaging investigations; thus, a great interest is focused on blood isoforms of the phosphorylated Tau protein (pTau), indicators of ongoing tau pathology (i.e. neurofibrillary tangles, NFTs, an AD neuropathological hallmark) in the central nervous system (CNS). However, current data often highlight discordant results about the ability of blood pTau to predict CSF status. Objective: We aim to synthesise the studies that compared pTau levels on CSF and blood to assess their correlation in AD continuum. Methods: We performed a narrative literature review using, first, MEDLINE (via PubMed) by means of MeSH terms, and then, we expanded the reults by means of Scopus and Web of Sciences to be as inclusive as possible. Finally, we added work following an expert opinion. Only papers presenting original data on pTau values on both blood and CSF were included. Results: The 33 included studies show an extreme heterogeneity in terms of pTau isoform (pTau181, 217 and 231), laboratory methods, diagnostic criteria and choice of comparison groups. Most studies evaluated plasma pTau181, while data on other isoforms and serum are scarcer. Discussion: Most papers identify a correlation between CSF and blood measurements. Furthermore, even when not specified, it is often possible to show an increase in blood pTau values as AD-related damage progresses in the AD continuum and higher values in AD than in other neurodegenerative diseases. Notably, plasma pTau231 seems the first biomarker to look for in the earliest and pre-clinical stages, quickly followed by pTau217 and, finally, by pTau181. Conclusions: Our results encourage the use of blood pTau for the early identification of patients with AD continuum. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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8. A primer to vascular anatomy of the brain: an overview on anterior compartment.
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Morales-Roccuzzo, Diego, Sabahi, Mohammadmahdi, Obrzut, Michal, Najera, Edinson, Monterroso-Cohen, David, Bsat, Shadi, Adada, Badih, and Borghei-Razavi, Hamid
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BRAIN anatomy , *INTERNAL carotid artery , *ANTERIOR cerebral artery , *LITERATURE reviews , *VERTEBRAL artery , *CENTRAL nervous system - Abstract
Purpose: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. Method: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. Results: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. Conclusion: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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9. Task Force Paper On Cerebellar Transplantation: Are We Ready to Treat Cerebellar Disorders with Cell Therapy?
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Cendelin, Jan, Buffo, Annalisa, Hirai, Hirokazu, Magrassi, Lorenzo, Mitoma, Hiroshi, Sherrard, Rachel, Vozeh, Frantisek, and Manto, Mario
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TASK forces , *CELLULAR therapy , *CENTRAL nervous system , *TRANSPLANTATION of organs, tissues, etc. , *CENTRAL nervous system injuries , *DISEASES - Abstract
Restoration of damaged central nervous system structures, functional recovery, and prevention of neuronal loss during neurodegenerative diseases are major objectives in cerebellar research. The highly organized anatomical structure of the cerebellum with numerous inputs/outputs, the complexity of cerebellar functions, and the large spectrum of cerebellar ataxias render therapies of cerebellar disorders highly challenging. There are currently several therapeutic approaches including motor rehabilitation, neuroprotective drugs, non-invasive cerebellar stimulation, molecularly based therapy targeting pathogenesis of the disease, and neurotransplantation. We discuss the goals and possible beneficial mechanisms of transplantation therapy for cerebellar damage and its limitations and factors determining outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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10. Research Paper: Comparison of the Position Sense of the Knee Joint in Patients With Multiple Sclerosis and Healthy Controls.
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Aliabadi, Saina, Khanmohammadi, Roya, Olyaei, Gholamrezareza, Ghotbi, Nastaran, Talebian, Saeed, and Moghadasi, Abdolreza Naser
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PATIENTS , *MULTIPLE sclerosis , *CENTRAL nervous system , *PROPRIOCEPTION , *TUBEROUS sclerosis - Abstract
Introduction: Position sense, one of the most accurate senses in the body, makes everyone aware of the state of the body in space. This sense is an essential ability in maintaining physical health and avoiding injury. Deficits in position sense cause balance impairments in people with mild Multiple Sclerosis (MS). Position sense requires instant and coordinated communication between the central nervous system and peripheral nervous system, while in patients with MS, communication between the brain and other parts of the body is disrupted. This study aims to compare the position sense of knee joint in people with MS and healthy subjects. Materials and Methods: Ten healthy subjects with the Mean±SD age of 27.6±3.71 years and 10 persons with MS disease and the Mean±SD age of 31.40±3.50 years participated in this study. For evaluating their position sense of knee joint, they flexed their knees (from 90 to 45 degrees) four times, and then a software calculated their repositioning errors. Results: No significant changes in repositioning errors (constant, variable, absolute) were observed in MS patients, and the control group (P˃0.05). Conclusion: The results indicate that mild MS disease cannot disturb the position sense of knee joint. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. Aided Diagnosis Model Based on Deep Learning for Glioblastoma, Solitary Brain Metastases, and Primary Central Nervous System Lymphoma with Multi-Modal MRI.
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Liu, Xiao and Liu, Jie
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DEEP learning , *CENTRAL nervous system , *CINGULATE cortex , *CANCER diagnosis , *DIAGNOSIS , *MAGNETIC resonance imaging ,CENTRAL nervous system tumors - Abstract
Simple Summary: Diagnosing glioblastoma multiforme (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) in malignant tumors of the central nervous system using multi-modal magnetic resonance imaging (MRI) is significantly important in helping physicians develop treatment plans and enhance patient prognosis. In this paper, MFFC-Net is developed and validated using deep learning methods to predict these three tumor categories from multi-modal MRI without the manual region of interest (ROI). MFFC-Net first uses a multi-encoder with DenseBlocks to extract deep features from multi-modal MRI. Then, the feature fusion layer fuses the deep information between different modalities and tissues. Finally, the spatial-channel attention module suppresses redundant new information and activates tumor classification-related features. Compared with radiomics models, MFFC-Net demonstrated higher accuracy. In addition, the results in the different sequences provide important references for future clinical work on MRI image acquisition. We believe that MFFC-Net has the potential to assist in the diagnosis and treatment of brain tumors in the future. (1) Background: Diagnosis of glioblastoma (GBM), solitary brain metastases (SBM), and primary central nervous system lymphoma (PCNSL) plays a decisive role in the development of personalized treatment plans. Constructing a deep learning classification network to diagnose GBM, SBM, and PCNSL with multi-modal MRI is important and necessary. (2) Subjects: GBM, SBM, and PCNSL were confirmed by histopathology with the multi-modal MRI examination (study from 1225 subjects, average age 53 years, 671 males), 3.0 T T2 fluid-attenuated inversion recovery (T2-Flair), and Contrast-enhanced T1-weighted imaging (CE-T1WI). (3) Methods: This paper introduces MFFC-Net, a classification model based on the fusion of multi-modal MRIs, for the classification of GBM, SBM, and PCNSL. The network architecture consists of parallel encoders using DenseBlocks to extract features from different modalities of MRI images. Subsequently, an L 1 − n o r m feature fusion module is applied to enhance the interrelationships among tumor tissues. Then, a spatial-channel self-attention weighting operation is performed after the feature fusion. Finally, the classification results are obtained using the full convolutional layer (FC) and Soft-max. (4) Results: The ACC of MFFC-Net based on feature fusion was 0.920, better than the radiomics model (ACC of 0.829). There was no significant difference in the ACC compared to the expert radiologist (0.920 vs. 0.924, p = 0.774). (5) Conclusions: Our MFFC-Net model could distinguish GBM, SBM, and PCNSL preoperatively based on multi-modal MRI, with a higher performance than the radiomics model and was comparable to radiologists. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. The people behind the papers - Wael Noor El-Nachef and Marianne Bronner.
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ENTERIC nervous system , *NEURAL crest , *GASTROINTESTINAL system , *CENTRAL nervous system , *DEVELOPMENTAL biology - Published
- 2020
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13. HEALTHY AND DISEASED HUMAN BRAIN PROCESSING (short paper).
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Kotetishvili, Ketevan, Gogishvili, Anna, and Kobalia, Nino
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BRAIN imaging , *WHITE matter (Nerve tissue) , *NEUROSCIENCES , *CENTRAL nervous system , *NEURONS - Abstract
After scanning the patient, the data processing presented here follows. First, we must convert 'Dicom' files to 'nifti' files. Then, we need eddy correction (movement to correct distorted photos). After this we use B vectors correction and use MATLAB program, also we use MATLAB for PI, which means background noise correction. For masking we use FSL program, in order to obtain a correct size of brain and finally we use 'MainExploreDTI' to see the direction of fibers. [ABSTRACT FROM AUTHOR]
- Published
- 2018
14. How to Perform Intra-Operative Contrast-Enhanced Ultrasound of the Brain-A WFUMB Position Paper.
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Prada, Francesco, Vetrano, Ignazio G., Gennari, Antonio G., Mauri, Giovanni, Martegani, Alberto, Solbiati, Luigi, Sconfienza, Luca Maria, Quaia, Emilio, Kearns, Kathryn N., Kalani, M. Yashar S., Park, Min S., DiMeco, Francesco, and Dietrich, Christoph
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CONTRAST-enhanced ultrasound , *ULTRASOUND contrast media , *ULTRASONIC imaging - Abstract
Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Self-assembled dipeptide grafted nanohybrid material strips for reliable spectroscopic and electrochemical recognition of tryptamine.
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Divya, Saini, Sanjeev, Kalra, Sanchit, Kaur, Navneet, and Singh, Narinder
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TRYPTAMINE , *DIPEPTIDES , *FOODBORNE diseases , *BIOGENIC amines , *CENTRAL nervous system - Abstract
According to the World Health Organization (WHO), foods high in tryptamine may cause foodborne diseases and abnormal activity in the central nervous system (CNS). The real-time monitoring of tryptamine levels is an emphasized topic among scientific community. In the present work, we report a cost-effective fluorescent paper strips-based methodology impregnated with self-assembled dipeptide-modified (DM1) zinc oxide (ZnO) i.e. DM1@ZnO for the real-time monitoring of tryptamine levels. It is based on an organic-inorganic nanohybrid material of self-assembled N -functionalised dipeptide molecule coated over the surface of ZnO thus tailoring its properties for the detection of tryptamine employing spectroscopic and electrochemical methods. The designed material exhibited a noteworthy response towards tryptamine irrespective of the presence of other biogenic amines (BAs). It selectively displayed blue fluorescence under the 365 nm UV light. On top of that, the detection of tryptamine was also corroborated by its transition to 2-oxytryptamine, as deduced from its electrochemical route. Thus, the proposed paper strip-based methodology unbolts a realistic platform for the efficient recognition of varying levels of tryptamine thus tackling the prima facie reasons for foodborne diseases. [Display omitted] • Fabrication of self-assembled dipeptide-based nanohybrid material. • Spectroscopic and electrochemical recognition of tryptamine. • Interaction of DM1@ZnO with tryptamine and its electrochemical conversion to 2-oxytryptamine. • Fabrication of DM1@ZnO grafted fluorescent paper strips. • Realistic platform for the efficient recognition of tryptamine thus tackling the prima facie reasons for foodborne diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. The role of annexins in central nervous system development and disease.
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White II, Zachary B., Nair, Sindhu, and Bredel, Markus
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CENTRAL nervous system diseases , *ANNEXINS , *CENTRAL nervous system viral diseases , *ALZHEIMER'S disease , *CELL membranes , *CENTRAL nervous system ,CENTRAL nervous system tumors - Abstract
Annexins, a group of Ca2+-dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+-dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes. Annexins exhibit dynamic roles in neuronal development, influencing differentiation, proliferation, and synaptic formation in CNS tissues. Notably, annexins such as ANXA1 and ANXA2 play roles in apoptosis and blood-brain barrier (BBB) integrity. Neurological disorders, including Alzheimer's disease, multiple sclerosis, and depression, involve annexin dysregulation, influencing neuroinflammation, blood-brain barrier integrity, and stress responses. Moreover, annexins contribute to the pathogenesis of CNS tumors, either promoting or suppressing tumor growth, angiogenesis, and invasion. Annexin expression patterns vary across different CNS tumor types, providing potential prognostic markers and therapeutic targets. This review underscores the multifaceted roles of annexins in the CNS, highlighting their importance in normal functioning, disease progression, and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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17. Multifunctional roles of γ-enolase in the central nervous system: more than a neuronal marker.
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Horvat, Selena, Kos, Janko, and Pišlar, Anja
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CENTRAL nervous system , *ALZHEIMER'S disease , *SCAFFOLD proteins , *NEURONS , *NEUROLOGICAL disorders - Abstract
Enolase, a multifunctional protein with diverse isoforms, has generally been recognized for its primary roles in glycolysis and gluconeogenesis. The shift in isoform expression from α-enolase to neuron-specific γ-enolase extends beyond its enzymatic role. Enolase is essential for neuronal survival, differentiation, and the maturation of neurons and glial cells in the central nervous system. Neuron-specific γ-enolase is a critical biomarker for neurodegenerative pathologies and neurological conditions, not only indicating disease but also participating in nerve cell formation and neuroprotection and exhibiting neurotrophic-like properties. These properties are precisely regulated by cysteine peptidase cathepsin X and scaffold protein γ1-syntrophin. Our findings suggest that γ-enolase, specifically its C-terminal part, may offer neuroprotective benefits against neurotoxicity seen in Alzheimer's and Parkinson's disease. Furthermore, although the therapeutic potential of γ-enolase seems promising, the effectiveness of enolase inhibitors is under debate. This paper reviews the research on the roles of γ-enolase in the central nervous system, especially in pathophysiological events and the regulation of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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18. The Scope, Trends, and Challenges of Neurosurgical Research in Nigeria: A Bibliometric Review.
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Ukachukwu, Alvan-Emeka K., Ogundeji, Olaniyi D., Abu-Bonsrah, Nancy, Still, Megan E.H., Trillo-Ordonez, Yesel, Oboh, Ehita N., Nischal, Shiva A., Deng, Di D., Ugorji, Chiazam, Seas, Andreas, Badejo, Oluwakemi A., Malomo, Toluyemi A., Nwaribe, Evaristus E., Oyemolade, Toyin A., Okere, Oghenekevwe E., Oboh, Ena, Waguia-Kouam, Romaric, Rahman, Raphia, Asemota, Isaac, and Reddy, Ramya
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BIBLIOMETRICS , *BRAIN injuries , *CENTRAL nervous system , *EVIDENCE-based management , *MEDICAL research , *CENTRAL nervous system injuries , *GINGIVAL recession - Abstract
This study investigates the scope, trends, and challenges of neurosurgical research in Nigeria since inception of the specialty in 1962. A bibliometric review of the neurosurgical literature from Nigeria was performed. Variables extracted included year and journal of publication, article topic, article type, research type, study design, article focus area, and limitations. Descriptive and quantitative analyses were performed for all variables. Trends of research publications were described in three periods: pioneering (1962–1981), recession (1982–2001), and resurgent (2002–2021). Of the 1023 included articles, 10.0% were published in the pioneering period, 9.2% in the recession period, and 80.8% in the resurgent period. Papers were predominantly published in World Neurosurgery (4.5%) and Nigerian Journal of Clinical Practice (4.0%). A total of 79.9% of the 4618 authors were from Nigerian institutions; 86.3% of the articles covered clinical research and were mainly focused on service delivery and epidemiology (89.9%). The most prominent topics were traumatic brain injury (25.8%) and central nervous system malignancy (21.4%). Only 4.4% of the publications received funding, mostly from agencies in the United States (31.7%). Barriers to neurosurgical research included lack of clinical databases (18.0%), increasing burden of disease (12.5%), and diagnostic challenges (12.4%). Neurosurgical research in Nigeria continues to grow due to increased training, workforce, and infrastructural improvements. Addressing the major challenges through establishment of research databases, development of evidence-based management guidelines, and increasing research training, funding and opportunities can increase research capacity in Nigeria. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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19. HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.
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Thompson, Landon John-Patrick, Genovese, Jessica, Hong, Zhenzi, Singh, Meera Vir, and Singh, Vir Bahadur
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NEUROBEHAVIORAL disorders , *CELLULAR pathology , *BLOOD-brain barrier , *TAT protein , *HIV-1 glycoprotein 120 , *MOLECULAR pathology , *CENTRAL nervous system - Abstract
Despite combined antiretroviral therapy (cART) limiting HIV replication to undetectable levels in the blood, people living with HIV continue to experience HIV-associated neurocognitive disorder (HAND). HAND is associated with neurocognitive impairment, including motor impairment, and memory loss. HIV has been detected in the brain within 8 days of estimated exposure and the mechanisms for this early entry are being actively studied. Once having entered into the central nervous system (CNS), HIV degrades the blood–brain barrier through the production of its gp120 and Tat proteins. These proteins are directly toxic to endothelial cells and neurons, and propagate inflammatory cytokines by the activation of immune cells and dysregulation of tight junction proteins. The BBB breakdown is associated with the progression of neurocognitive disease. One of the main hurdles for treatment for HAND is the latent pool of cells, which are insensitive to cART and prolong inflammation by harboring the provirus in long-lived cells that can reactivate, causing damage. Multiple strategies are being studied to combat the latent pool and HAND; however, clinically, these approaches have been insufficient and require further revisions. The goal of this paper is to aggregate the known mechanisms and challenges associated with HAND. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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20. Reliability analysis for command‐and‐control systems based on edge extension diagram and binary decision diagram.
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Li, Yifan, Huang, Hong‐Zhong, Zhang, Tingyu, Huang, Sizhe, and Li, Yahua
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INFORMATION warfare , *CENTRAL nervous system , *PROBLEM solving - Abstract
As the central nervous system of modern information warfare, the command‐and‐control network becomes the brain of command and the strategic target of the enemy's primary attack during the operation. In this paper, a method based on edge extension diagram (EED) and binary decision diagram (BDD) is proposed to evaluate the reliability of connectivity within the basic command post of command‐and‐control network, which is solving the problem that the conventional methods failed to model failure probabilities of node links and with low calculation efficiency. First, graph simplification of network topology, extension of nodes under reliable state, construction of path functions, replacement of associated edges, variable sorting, construction of binary decision graphs, and recursive calculation to evaluate the reliability of the connection between the two ends of the command‐and‐control network. Then, further analyze and sort the variable importance of the command‐and‐control network and analyze the sensitivity of the network topology. This paper contributes to the reliability assessment of command‐and‐control network system, the identification and maintenance of key network nodes, and the design of network topology structure. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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21. The Canadian Breast Cancer Symposium 2023 Meeting Report.
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Cil, Tulin, Boileau, Jean-François, Chia, Stephen, DeCoteau, MJ, Jerzak, Katarzyna J., Koch, Anne, Nixon, Nancy, Quan, May Lynn, Roberts, Amanda, and Brezden-Masley, Christine
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BREAST cancer , *MEDICAL personnel , *CENTRAL nervous system , *ONCOLOGIC surgery , *DUCTAL carcinoma , *CARCINOMA in situ , *EXPERIMENTAL medicine , *ONCOLOGY nursing - Abstract
On 15–16 June 2023, healthcare professionals and breast cancer patients and advocates from across Canada met in Toronto, Ontario, for the 2023 Canadian Breast Cancer Symposium (CBSC.). The CBSC. is a national, multidisciplinary event that occurs every 2 years with the goal of developing a personalized approach to the management of breast cancer in Canada. Experts provided state-of-the-art information to help optimally manage breast cancer patients, including etiology, prevention, diagnosis, experimental biology, and therapy of breast cancer and premalignant breast disease. The symposium also had the objectives of increasing communication and collaboration among breast cancer healthcare providers nationwide and providing a comprehensive and real-life review of the many facets of breast cancer. The sessions covered the patient voice, the top breast cancer papers from different disciplines in 2022, artificial intelligence in breast cancer, systemic therapy updates, the management of central nervous system metastases, multidisciplinary management of ductal carcinoma in situ, special populations, optimization-based individual prognostic factors, toxicity management of novel therapeutics, survivorship, and updates in surgical oncology. The key takeaways of these sessions have been summarized in this conference report. [ABSTRACT FROM AUTHOR]
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- 2024
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22. The Development of a New Patient-Reported Outcome Measure in Recessive Ataxias: The Person-Reported Ataxia Impact Scale.
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Tremblay, Marjolaine, Brais, Bernard, Asselin, Véronique, Buffet, Martin, Girard, André, Girard, Denis, Berbiche, Djamal, and Gagnon, Cynthia
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ATAXIA , *PERIPHERAL nervous system , *TEST validity , *NEUROLOGICAL disorders , *CENTRAL nervous system - Abstract
Autosomal recessive cerebellar ataxias (ARCAs) are inherited neurological disorders that can affect both the central and peripheral nervous systems. To assess the effects of interventions according to the perception of people affected, patient-reported outcome measures (PROMs) must be available. This paper presents the development process of the Person-Reported Ataxia Impact Scale (PRAIS), a new PROM in recessive ataxias, and the documentation of its content validity, interpretability, and construct validity (structural and discriminant). The development followed the PROMIS framework and the Food and Drug Administration guidelines. A mixed-method study design was used to develop the PROM. A systematic review of the literature, semistructured interviews, and discussion groups was conducted to constitute an item pool. Experts' consultation helped formulate items, and the questionnaire was sent online to be completed by people affected. Statistical analyses were performed to assess the structural and discriminant validity. A total of 125 people affected by recessive ataxia completed the questionnaire. The factor analysis confirmed the three components: physical functions and activities, mental functions, and social functions. The statistical analysis showed that it can discriminate between stages of mobility and level of autonomy. It showed very good levels of internal consistency (0.79 to 0.89). The Person-Reported Ataxia Impact Scale (PRAIS) is a 38-item questionnaire that assesses the manifestations and impacts of the disease according to the perception of people affected by recessive ataxia. It can be used in clinical and research settings. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Procyanidins and sensory nutrition; do procyanidins modulate homeostasis via astringent taste receptors?
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Osakabe, Naomi, Fushimi, Taiki, Fujii, Yasuyuki, and Calabrese, Vittorio
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TASTE receptors , *PROCYANIDINS , *HOMEOSTASIS , *NEUROENDOCRINE system , *CENTRAL nervous system , *NUTRITION - Abstract
Long-term intake of procyanidins has been suggested to reduce the risk of cardiovascular disease, dementia, and sensory function decline associated with aging. However, most of the ingested procyanidins are not absorbed and are excreted in the feces, so the mechanism of their beneficial impact is unknown. Procyanidins are the components of astringency in plant foods and their stimulation appears to be directly transmitted to the central nervous system via sensory nerves. Recent attention has been focused on the taste receptors expressed in the extra-oral gastrointestinal tract may regulate homeostasis via the neuroendocrine system. In this paper, we have reviewed recent findings on the relationship between the astringency of procyanidins and their bioregulatory effects. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Amide proton transfer-weighted imaging of the abdomen: Current progress and future directions.
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Sheng, Liuji, Yuan, Enyu, Yuan, Fang, and Song, Bin
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PROTONS , *MAGNETIZATION transfer , *ALZHEIMER'S disease , *CENTRAL nervous system , *STROKE - Abstract
The chemical exchange saturation transfer technique serves as a valuable tool for generating in vivo image contrast based on the content of various proton groups, including amide protons, amine protons, and aliphatic protons. Among these, amide proton transfer-weighted (APTw) imaging has seen extensive development as a means to assess the biochemical status of lesions. The exchange from saturated amide protons to bulk water protons during and following the saturation ratio frequency pulse contributes to detectable APT signals. While APTw imaging has garnered significant attention in the central nervous system, demonstrating noteworthy findings in cerebral neoplasia, stroke, and Alzheimer's disease over the past decade, its application in the abdomen has been a relatively recent progression. Notably, studies have explored its utility in hepatocellular carcinoma, prostate cancer, and cervical carcinoma within the abdominal context. Despite these advancements, there is a paucity of reviews on APTw imaging in abdominal applications. This paper aims to fill this gap by providing a concise overview of the fundamental theories underpinning APTw imaging. Additionally, we systematically summarize its diverse clinical applications in the abdomen, with a particular focus on the digestive and urogenital systems. Finally, the manuscript concludes by discussing technical limitations and factors influencing APTw imaging in abdominal applications, along with prospects for future research. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Annual Research Review: Neuroimmune network model of depression: a developmental perspective.
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Nusslock, Robin, Alloy, Lauren B., Brody, Gene H., and Miller, Gregory E.
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PREVENTION of mental depression , *BRAIN anatomy , *EMOTION regulation , *CELL communication , *MONOCYTES , *NEURAL pathways , *NEUROPHYSIOLOGY , *BRAIN , *CELLULAR immunity , *CENTRAL nervous system , *ANHEDONIA , *NEUROLOGICAL disorders , *NEUROBIOLOGY , *AUTOIMMUNE diseases , *INFLAMMATION , *DRUGS , *CYTOKINES , *MENTAL depression , *IMMUNITY , *NEUROTRANSMITTERS , *ADVERSE childhood experiences , *ADOLESCENCE ,BRAIN metabolism - Abstract
Depression is a serious public health problem, and adolescence is an 'age of risk' for the onset of Major Depressive Disorder. Recently, we and others have proposed neuroimmune network models that highlight bidirectional communication between the brain and the immune system in both mental and physical health, including depression. These models draw on research indicating that the cellular actors (particularly monocytes) and signaling molecules (particularly cytokines) that orchestrate inflammation in the periphery can directly modulate the structure and function of the brain. In the brain, inflammatory activity heightens sensitivity to threats in the cortico‐amygdala circuit, lowers sensitivity to rewards in the cortico‐striatal circuit, and alters executive control and emotion regulation in the prefrontal cortex. When dysregulated, and particularly under conditions of chronic stress, inflammation can generate feelings of dysphoria, distress, and anhedonia. This is proposed to initiate unhealthy, self‐medicating behaviors (e.g. substance use, poor diet) to manage the dysphoria, which further heighten inflammation. Over time, dysregulation in these brain circuits and the inflammatory response may compound each other to form a positive feedback loop, whereby dysregulation in one organ system exacerbates the other. We and others suggest that this neuroimmune dysregulation is a dynamic joint vulnerability for depression, particularly during adolescence. We have three goals for the present paper. First, we extend neuroimmune network models of mental and physical health to generate a developmental framework of risk for the onset of depression during adolescence. Second, we examine how a neuroimmune network perspective can help explain the high rates of comorbidity between depression and other psychiatric disorders across development, and multimorbidity between depression and stress‐related medical illnesses. Finally, we consider how identifying neuroimmune pathways to depression can facilitate a 'next generation' of behavioral and biological interventions that target neuroimmune signaling to treat, and ideally prevent, depression in youth and adolescents. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.
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Xu, Nuo, Gong, Peng, Xu, Shiting, Chen, Yangyun, Dai, Mengyuan, Jia, Zhaoxing, and Lin, Xianming
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BLOOD-brain barrier , *GLIAL fibrillary acidic protein , *ELECTROACUPUNCTURE , *VASCULAR endothelial growth factors , *NERVE growth factor , *CENTRAL nervous system - Abstract
An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Synthesis and Characterization of ZIF-90 Nanoparticles as Potential Brain Cancer Therapy.
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Monarca, Lorenzo, Ragonese, Francesco, Sabbatini, Paola, Caglioti, Concetta, Stamegna, Matteo, Palazzetti, Federico, Sportoletti, Paolo, Costantino, Ferdinando, and Fioretti, Bernard
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BRAIN cancer , *CANCER treatment , *NANOPARTICLES , *CENTRAL nervous system , *DRUG therapy - Abstract
Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Navigating the Nose-to-Brain Route: A Systematic Review on Lipid-Based Nanocarriers for Central Nervous System Disorders.
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Agosti, Edoardo, Zeppieri, Marco, Antonietti, Sara, Battaglia, Luigi, Ius, Tamara, Gagliano, Caterina, Fontanella, Marco Maria, and Panciani, Pier Paolo
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CENTRAL nervous system , *INTRANASAL administration , *NANOCARRIERS , *BLOOD-brain barrier , *ALZHEIMER'S disease , *INTRANASAL medication , *LIPIDS - Abstract
Background: The blood–brain barrier (BBB) regulates brain substance entry, posing challenges for treating brain diseases. Traditional methods face limitations, leading to the exploration of non-invasive intranasal drug delivery. This approach exploits the direct nose-to-brain connection, overcoming BBB restrictions. Intranasal delivery enhances drug bioavailability, reduces dosage, and minimizes systemic side effects. Notably, lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, offer advantages like improved stability and controlled release. Their nanoscale size facilitates efficient drug loading, enhancing solubility and bioavailability. Tailored lipid compositions enable optimal drug release, which is crucial for chronic brain diseases. This review assesses lipid nanoparticles in treating neuro-oncological and neurodegenerative conditions, providing insights for effective nose-to-brain drug delivery. Methods: A systematic search was conducted across major medical databases (PubMed, Ovid MEDLINE, and Scopus) up to 6 January 2024. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "lipid nanoparticles", "intranasal administration", "neuro-oncological diseases", and "neurodegenerative disorders". This review consists of studies in vitro, in vivo, or ex vivo on the intranasal administration of lipid-based nanocarriers for the treatment of brain diseases. Results: Out of the initial 891 papers identified, 26 articles met the eligibility criteria after a rigorous analysis. The exclusion of 360 articles was due to reasons such as irrelevance, non-reporting selected outcomes, the article being a systematic literature review or meta-analysis, and lack of method/results details. This systematic literature review, focusing on nose-to-brain drug delivery via lipid-based nanocarriers for neuro-oncological, neurodegenerative, and other brain diseases, encompassed 60 studies. A temporal distribution analysis indicated a peak in research interest between 2018 and 2020 (28.3%), with a steady increase over time. Regarding drug categories, Alzheimer's disease was prominent (26.7%), followed by antiblastic drugs (25.0%). Among the 65 drugs investigated, Rivastigmine, Doxorubicin, and Carmustine were the most studied (5.0%), showcasing a diverse approach to neurological disorders. Notably, solid lipid nanoparticles (SLNs) were predominant (65.0%), followed by nanostructured lipid carriers (NLCs) (28.3%), highlighting their efficacy in intranasal drug delivery. Various lipids were employed, with glyceryl monostearate being prominent (20.0%), indicating preferences in formulation. Performance assessment assays were balanced, with in vivo studies taking precedence (43.3%), emphasizing the translation of findings to complex biological systems for potential clinical applications. Conclusions: This systematic review reveals the transformative potential of intranasal lipid nanoparticles in treating brain diseases, overcoming the BBB. Positive outcomes highlight the effectiveness of SLNs and NLCs, which are promising new approaches for ailments from AD to stroke and gliomas. While celebrating progress, addressing challenges like nanoparticle toxicity is also crucial. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Application of artificial intelligence in HE risk prediction modelling and research advances.
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HUANG Liangji-ang, MAO Dewen, ZHENG Jinghui, WANG Minggang, and YAO Chun
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ARTIFICIAL intelligence , *HEPATIC encephalopathy , *PREDICTION models , *CENTRAL nervous system , *BRAIN diseases - Abstract
Hepatic encephalopathy is a clinical syndrome of central nervous system dysfunction caused by liver insufficiency. It severely affects the quality of life of patients and may lead to death. Accurate prediction of the risk of developing hepatic encephalopathy is crucial for early intervention and treatment. In order to identify the risk of hepatic encephalopathy in patients in advance, many studies have been devoted to efforts to develop tools and methods to identify the risk of hepatic encephalopathy as early as possible, so as to develop preventive and early management strategies. Most conventional hepatic encephalopathy risk prediction models currently assess the probability of a patient developing hepatic encephalopathy by analysing factors such as clinical data and biochemical indicators, however, their accuracy, sensitivity and positive predictive value are not high. The application of artificial intelligence to clinical predictive modelling is a very hot and promising area, which can use large amounts of data and complex algorithms to improve the accuracy and efficiency of diagnosis and prognosis. To date, there have been few studies using AI techniques to predict hepatic encephalopathy. Therefore, this paper reviews the research progress of hepatic encephalopathy risk prediction models, and also discusses the prospect of AI application in hepatic encephalopathy risk prediction models. It also points out the challenges and future research directions of AI in HE risk prediction model research in order to promote the development and clinical application of hepatic encephalopathy risk prediction models. [ABSTRACT FROM AUTHOR]
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- 2024
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30. Photobiomodulation for Neurodegenerative Diseases: A Scoping Review.
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Shen, Qi, Guo, Haoyun, and Yan, Yihua
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NEURODEGENERATION , *PHOTOBIOMODULATION therapy , *ALZHEIMER'S disease , *PARKINSON'S disease , *CENTRAL nervous system - Abstract
Neurodegenerative diseases involve the progressive dysfunction and loss of neurons in the central nervous system and thus present a significant challenge due to the absence of effective therapies for halting or reversing their progression. Based on the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which have prolonged incubation periods and protracted courses, exploring non-invasive physical therapy methods is essential for alleviating such diseases and ensuring that patients have an improved quality of life. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits and functions by stimulating, healing, regenerating, and protecting organizations at risk of injury, degradation, or death. Over the last two decades, PBM has gained widespread recognition as a non-invasive physical therapy method, showing efficacy in pain relief, anti-inflammatory responses, and tissue regeneration. Its application has expanded into the fields of neurology and psychiatry, where extensive research has been conducted. This paper presents a review and evaluation of studies investigating PBM in neurodegenerative diseases, with a specific emphasis on recent applications in AD and PD treatment for both animal and human subjects. Molecular mechanisms related to neuron damage and cognitive impairment are scrutinized, offering valuable insights into PBM's potential as a non-invasive therapeutic strategy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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31. Toxicologic Neuropathology of Novel Biotherapeutics.
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Bangari, Dinesh S., Lanigan, Lisa G., Cramer, Sarah D., Grieves, Jessica L., Meisner, René, Rogers, Arlin B., Galbreath, Elizabeth J., and Bolon, Brad
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NEUROLOGICAL disorders , *CENTRAL nervous system , *GENOME editing , *GENE therapy , *NUCLEIC acids - Abstract
Biotherapeutic modalities such as cell therapies, gene therapies, nucleic acids, and proteins are increasingly investigated as disease-modifying treatments for severe and life-threatening neurodegenerative disorders. Such diverse bio-derived test articles are fraught with unique and often unpredictable biological consequences, while guidance regarding nonclinical experimental design, neuropathology evaluation, and interpretation is often limited. This paper summarizes key messages offered during a half-day continuing education course on toxicologic neuropathology of neuro-targeted biotherapeutics. Topics included fundamental neurobiology concepts, pharmacology, frequent toxicological findings, and their interpretation including adversity decisions. Covered biotherapeutic classes included cell therapies, gene editing and gene therapy vectors, nucleic acids, and proteins. If agents are administered directly into the central nervous system, initial screening using hematoxylin and eosin (H&E)-stained sections of currently recommended neural organs (brain [7 levels], spinal cord [3 levels], and sciatic nerve) may need to expand to include other components (e.g., more brain levels, ganglia, and/or additional nerves) and/or special neurohistological procedures to characterize possible neural effects (e.g., cell type-specific markers for reactive glial cells). Scientists who evaluate the safety of novel biologics will find this paper to be a practical reference for preclinical safety testing and risk assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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32. Distribution of Monocarboxylate Transporters in Brain and Choroid Plexus Epithelium.
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Ueno, Masaki, Chiba, Yoichi, Murakami, Ryuta, Miyai, Yumi, Matsumoto, Koichi, Wakamatsu, Keiji, Takebayashi, Genta, Uemura, Naoya, and Yanase, Ken
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MONOCARBOXYLATE transporters , *CHOROID plexus , *GLUCOSE transporters , *EPITHELIUM , *CENTRAL nervous system - Abstract
The choroid plexus (CP) plays central roles in regulating the microenvironment of the central nervous system by secreting the majority of cerebrospinal fluid (CSF) and controlling its composition. A monolayer of epithelial cells of CP plays a significant role in forming the blood–CSF barrier to restrict the movement of substances between the blood and ventricles. CP epithelial cells are equipped with transporters for glucose and lactate that are used as energy sources. There are many review papers on glucose transporters in CP epithelial cells. On the other hand, distribution of monocarboxylate transporters (MCTs) in CP epithelial cells has received less attention compared with glucose transporters. Some MCTs are known to transport lactate, pyruvate, and ketone bodies, whereas others transport thyroid hormones. Since CP epithelial cells have significant carrier functions as well as the barrier function, a decline in the expression and function of these transporters leads to a poor supply of thyroid hormones as well as lactate and can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases. In this review paper, recent findings regarding the distribution and significance of MCTs in the brain, especially in CP epithelial cells, are summarized. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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33. Autoimmune Encephalitis with Antibodies: Anti-NMDAR, Anti-AMPAR, Anti-GQ1b, Anti-DPPX, Anti-CASPR2, Anti-LGI1, Anti-RI, Anti-Yo, Anti-Hu, Anti-CV2 and Anti-GABAAR, in the Course of Psychoses, Neoplastic Diseases, and Paraneoplastic Syndromes.
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Braczkowski, Michał, Soszyński, Dariusz, Sierakowska, Alicja, Braczkowski, Ryszard, Kufel, Klaudia, and Łabuz-Roszak, Beata
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ANTI-NMDA receptor encephalitis , *PARANEOPLASTIC syndromes , *PSYCHOSES , *CELL surface antigens , *CENTRAL nervous system , *GLUTAMATE receptors - Abstract
Encephalitis is a condition with a variety of etiologies, clinical presentations, and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self-antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases, and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process. Strategy and Methodology: The articles on which the following paper was based were searched using search engines such as PubMed and Medline. Considering that anti-NMDAR antibodies were first described in 2007, the articles were from 2007 to 2023. The selection of papers was made by entering the phrases "autoimmune encephalitis and psychosis/paraneplastic syndromes or cancer". The total number of articles that could be searched was 747, of which 100 items were selected, the most recent reports illustrating the presented topic. Thirty-four of them were rejected in connection with case reports or papers that could not be accessed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. Gamma Loop Dysfunction as a Possible Neurophysiological Mechanism of Arthrogenic Muscle Inhibition: A Narrative Review of the Literature.
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Yu Konishi, Ryo Yoshii, and Ingersoll, Christopher D.
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SKELETAL muscle physiology , *SKELETAL muscle injuries , *NEURAL pathways , *REFLEXES , *MUSCLE strength , *QUADRICEPS muscle , *PROFESSIONAL competence , *CENTRAL nervous system - Abstract
Context: Quadriceps activation failure has been observed following various pathological conditions in a knee joint such as knee surgery, pain, effusion in knee, and osteoarthritis also could be aging matter. Those patients are unable to attain maximal quadriceps strength for a long period of time although their quadriceps itself is not damaged. This impairment is termed arthrogenic muscle inhibition CAMI). AMI has been of concern to clinicians because this weakness hinders the rehabilitation process considerably and delays recovery because strengthening protocols for the AMI could be largely ineffective. Clinically, it is important to understand neurophysiological mechanisms of the AMI to treat patients with the impairment. Objectives: This is a narrative review of the literature. The purpose of this review is to understand the following: (1) Why investigations of only peripheral spinal reflexive pathways are not enough for elucidation of the mechanisms of the AMI? (2) What we know about the role of the gamma spindle system in AMI so far? (3) Could a dysfunctional gamma spindle system contribute to AMI lead neural changes in upper central nervous system? and (4) Concerns that a clinician should take into consideration when deciding whether to apply therapeutic interventions for AMI. Data Sources: The databases PubMed. MEDLINE, SPORTDiscus, and CINAHL were searched with the terms arthrogenic muscle inhibition (AMI), reflex inhibition, joint mechanoreceptor, gamma loop, corticospinal pathway, spinal reflex, effusion, and joint injury. The remaining citations were collected from references of similar papers. Conclusions: AMI is a limiting factor in the rehabilitation of joint injury. Motor unit recruitment could be hindered in patients with AMI as a result of a dysfunctional gamma spindle system. Clinicians should understand the mechanism of AMI well in order to establish effective rehabilitation programs for AMI. Indeed, AMI is not caused by a single factor, but rather, multiple neural factors can change over time following the appearance of AMI. Therefore, multiple interventions targeting different neural pathways should be combined to achieve the ideal therapeutic goal for the treatment of AML [ABSTRACT FROM AUTHOR]
- Published
- 2022
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35. ‘ An investigation of the nervous control of defecation’ by Denny-Brown and Robertson: a classic paper revisited.
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Vilensky, J A., Bell, D.R., and Gilman, S.
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DEFECATION disorders , *NEUROLOGY , *CENTRAL nervous system , *SPHINCTERS - Abstract
In 1935 two young neurologists, Derek Denny-Brown and E. Graeme Robertson, published an article explaining the mechanisms underlying human defaecation based on a manometric study in patients with sacral root and spinal cord lesions, and normal subjects. This article is still routinely cited in studies of rectal and sphincter ani function. Unfortunately, however, the article itself is not written well, being composed of long convoluted sentences and containing 79 often indecipherable figures. Difficult-to-understand articles were common to the publications of Denny-Brown, who became one of the most prominent neurologists of the twentieth century. In accord with our prior work explaining Denny-Brown and Robertson's earlier paper on micturition, we provide here what we hope is a clear explanation of the methods and results in their study on defaecation. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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36. The neurovascular syndromes: A review of pathophysiology - Lessons learnt from Prof. Chandy's paper published in 1989.
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Bhatoe, Harjinder and Bhatoe, Harjinder S
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ACOUSTIC nerve , *PERIPHERAL nervous system , *FACIAL pain , *NEUROANATOMY , *TRIGEMINAL neuralgia , *CENTRAL nervous system , *NEUROSCIENCES , *ENTRAPMENT neuropathies ,VASCULAR disease diagnosis - Abstract
The article focuses on the study of neurovascular syndromes. It mentions that pulsatile propulsion of blood through blood vessels help in the circulation and transport of oxygen and nutrients. It mentions that pulsatile impulse by the heart in the cardiac cycle improves the pressure-related events to capillaries.
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- 2019
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37. Exercise and Weight Management: The Role of Leptin—A Systematic Review and Update of Clinical Data from 2000–2022.
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de Assis, Gilmara Gomes and Murawska-Ciałowicz, Eugenia
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LEPTIN , *REGULATION of body weight , *ADIPOSE tissues , *INGESTION disorders , *LEPTIN receptors , *CENTRAL nervous system - Abstract
A well-balanced metabolism means a lower risk for metabolism-related neuropsychiatric disorders. Leptin is a secretory adipokine involved in the central control of appetite that appears to play a role in the etiology of feeding-related disorders. Additionally, the influence of exercise on feeding behaviors potentially modulates the circulation of metabolites that signal through the central nervous system. In this systematic review, we collected the recent clinical evidence on the effect of exercise on leptin concentrations in health individuals published from 2000 to 20 September 2022, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA 2020 statement). Six hundred and thirty-eight papers were retrieved and forty-eight papers were included in the qualitative synthesis. Data supports that exercise positively influences appetite via enhancing peripheral and central leptin signaling (reuptake), especially during weight loss. Exercise modulation of leptin signaling through leptin receptors helps to stabilize increases in food intake during periods of negative energy balance, prior to a decrease in the body fat tissue content. At a high intensity, exercise appears to counteract leptin resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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38. The Brain's Glymphatic System: Drawing New Perspectives in Neuroscience.
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Ciurea, Alexandru Vlad, Mohan, Aurel George, Covache-Busuioc, Razvan-Adrian, Costin, Horia Petre, and Saceleanu, Vicentiu Mircea
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ALZHEIMER'S disease , *CENTRAL nervous system , *NEUROSCIENCES , *CIRCADIAN rhythms , *CEREBROSPINAL fluid , *BRAIN imaging , *CHRONIC traumatic encephalopathy - Abstract
This paper delves into the intricate structure and functionality of the brain's glymphatic system, bringing forth new dimensions in its neuroscientific understanding. This paper commences by exploring the cerebrospinal fluid (CSF)—its localization, production, and pivotal role within the central nervous system, acting as a cushion and vehicle for nutrient distribution and waste elimination. We then transition into an in-depth study of the morphophysiological aspects of the glymphatic system, a recent discovery revolutionizing the perception of waste clearance from the brain, highlighting its lymphatic-like characteristics and remarkable operations. This paper subsequently emphasizes the glymphatic system's potential implications in Alzheimer's disease (AD), discussing the connection between inefficient glymphatic clearance and AD pathogenesis. This review also elucidates the intriguing interplay between the glymphatic system and the circadian rhythm, illustrating the optimal functioning of glymphatic clearance during sleep. Lastly, we underscore the hitherto underappreciated involvement of the glymphatic system in the tumoral microenvironment, potentially impacting tumor growth and progression. This comprehensive paper accentuates the glymphatic system's pivotal role in multiple domains, fostering an understanding of the brain's waste clearance mechanisms and offering avenues for further research into neuropathological conditions. [ABSTRACT FROM AUTHOR]
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- 2023
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39. Central neuromodulators in mitigating functional gastrointestinal disorders: Mechanism and Effectiveness.
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Kumari, Soni, Das, Saumya, and Mishra, Apporva
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SEROTONIN uptake inhibitors , *ANTIDEPRESSANTS , *TRICYCLIC antidepressants , *CENTRAL nervous system , *GUT microbiome , *MENTAL illness - Abstract
In Functional gastrointestinal disorders, there is a paucity of knowledge regarding the fundamental physical and chemical anomalies, thus it can be solely diagnosed by symptomatology. They are triggered by gastrointestinal problems like changes in gut permeability, propulsion, gut flora, immunological response, and central nervous system function. The patient's nonadaptive behaviors, anxiety and concurrent psychiatric disorders all make these symptoms worse and result in long-lasting symptoms that affect the entire gut, such as discomfort, indigestion, and disturbed bowel habits. A biopsychosocial approach to management entails dietary and nutritional adjustments, modifications in lifestyle recommendations, and the use of medicine to address underlying pathophysiology. Functional gastrointestinal disorders are treated with antidepressants, antipsychotics and various medications that target the central nervous system. These drugs are now referred to as neuromodulators. Patients may benefit from using tricyclic antidepressants, selective serotonin reuptake inhibitors, and various central neuromodulators, but there are also risks involved. The different approaches to treat functional gastrointestinal problems are described in this review paper. The various negative effects of central neuromodulators as well as the processes by which they operate, the distinctions between the various classes and types of agents, and how they differ from one another are discussed in this paper. [ABSTRACT FROM AUTHOR]
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- 2023
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40. RESEARCH PAPER:Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
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Shkumatava, Alena, Stark, Alexander, Sive, Hazel, and Bartel, David P.
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MESSENGER RNA , *GENE expression , *RNA synthesis , *FLOW cytometry , *VERTEBRATES , *CENTRAL nervous system - Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that direct post-transcriptional repression of protein-coding genes. In vertebrates, each highly conserved miRNA typically regulates hundreds of target mRNAs. However, the precise relationship between expression of the miRNAs and that of their targets has remained unclear, in part because of the scarcity of quantitative expression data at cellular resolution. Here we report quantitative analyses of mRNA levels in miRNA-expressing cells of the zebrafish embryo, capturing entire miRNA expression domains, purified to cellular resolution using fluorescent-activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted targets that responded to the miRNAs and distinguished miRNA-mediated mRNA destabilization from other regulatory effects. For all three miRNAs examined, expression of the miRNAs and that of their predicted targets usually overlapped. A few targets were expressed at higher levels in miRNA-expressing cells than in the rest of the embryo, demonstrating that miRNA-mediated repression can act in opposition to other regulatory processes. However, for most targets expression was lower in miRNA-expressing cells than in the rest of the embryo, indicating that miRNAs usually operate in concert with the other regulatory machinery of the cell. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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41. Expression of the neuropeptide Y Y1 receptor in the CNS of rat and of wild-type and Y1 receptor knock-out mice. Focus on immunohistochemical localization1<FN ID="FN1"><NO>1</NO>This paper is dedicated to our collaborator and coauthor, the late John H. Walsh, an excellent and generous scientist and a fine human being.</FN>
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Kopp, J., Xu, Z.-Q., Zhang, X., Pedrazzini, T., Herzog, H., Kresse, A., Wong, H., Walsh, J.H., and Hökfelt, T.
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NEUROPEPTIDE Y , *ETHYLENEDIAMINETETRAACETIC acid , *CENTRAL nervous system , *IMMUNOFLUORESCENCE - Abstract
The distribution of neuropeptide Y (NPY) Y1 receptor-like immunoreactivity (Y1R-LI) has been studied in detail in the CNS of rat using a rabbit polyclonal antibody against the C-terminal 13 amino acids of the rat receptor protein. The indirect immunofluorescence technique with tyramide signal amplification has been employed. For specificity and comparative reasons Y1 knock-out mice and wild-type controls were analyzed. The distribution of Y1R mRNA was also studied using in situ hybridization. A limited comparison between Y1R-LI and NPY-LI was carried out.A widespread and abundant distribution of Y1R-LI, predominantly in processes but also in cell bodies, was observed. In fact, Y1R-LI was found in most regions of the CNS with a similar distribution pattern between rat and wild-type mouse. This staining was specific in the sense that it was absent in adjacent sections following preadsorption of the antibody with 10−5 M of the antigenic peptide, and that it could not be observed in sections of the Y1 KO mouse. In contrast, the staining obtained with an N-terminally directed Y1R antiserum did not disappear, strongly suggesting unspecificity. In brief, very high levels of Y1R-LI were seen in the islands of Calleja, the anterior olfactory nucleus, the molecular layer of the dentate gyrus, parts of the habenula, the interpeduncular nucleus, the mammillary body, the spinal nucleus of the trigeminal, caudal part, the paratrigeminal nucleus, and superficial layers of the dorsal horn. High levels were found in most cortical areas, many thalamic nuclei, some subnuclei of the amygdaloid complex, the hypothalamus and the nucleus of the stria terminalis, the nucleus of the solitary tract, the parabrachial nucleus, and the inferior olive. Moderate levels of Y1R-LI were detected in the cornu Ammonis and the subicular complex, many septal, some thalamic and many brainstem regions. Y1R staining of processes, often fiber and/or dot-like, and occasional cell bodies was also seen in tracts, such as the lateral lemniscus, the rubrospinal tract and the spinal tract of the trigeminal. There was in general a good overlap between Y1R-LI and NPY-LI, but some exceptions were found. Thus, some areas had NPY innervation but apparently lacked Y1Rs, whereas in other regions Y1R-LI, but no or only few NPY-positive nerve endings could be detected.Our results demonstrate that NPY signalling through the Y1R is common in the rat (and mouse) CNS. Mostly the Y1R is postsynaptic but there are also presynaptic Y1Rs. Mostly there is a good match between NPY-releasing nerve endings and Y1Rs, but ‘volume transmission’ may be ‘needed’ in some regions. Finally, the importance of using proper control experiments for immunohistochemical studies on seven-transmembrane receptors is stressed. [Copyright &y& Elsevier]
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- 2002
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42. Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.
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Czyżewski, Wojciech, Mazurek, Marek, Sakwa, Leon, Szymoniuk, Michał, Pham, Jennifer, Pasierb, Barbara, Litak, Jakub, Czyżewska, Ewa, Turek, Michał, Piotrowski, Bartłomiej, Torres, Kamil, and Rola, Radosław
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BRAIN injuries , *DRUG target , *CONNEXIN 43 , *MONOCLONAL antibodies , *CENTRAL nervous system , *NEURAL stem cells , *NERVE tissue - Abstract
Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Central nervous system clear cell meningioma: a systematic literature review.
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Liang, Qi, Ge, Pengfei, Liu, Yanhua, Zhu, Xiaoxi, Lu, Shan, Pan, Chengliang, Ji, Zhilin, Wang, Qingxuan, and Wang, Yubo
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CENTRAL nervous system , *MENINGIOMA , *PROGNOSIS , *SKULL base , *SYMPTOMS - Abstract
Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma. [ABSTRACT FROM AUTHOR]
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- 2024
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44. The modulatory role of gut microbiota on host behavior: exploring the interaction between the brain-gut axis and the neuroendocrine system.
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Awe, Temitope, Fasawe, Ayoola, Sawe, Caleb, Ogunware, Adedayo, Jamiu, Abdullahi Temitope, and Allen, Michael
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GUT microbiome , *NEUROENDOCRINE system , *MICROBIAL communities , *CENTRAL nervous system , *GASTROINTESTINAL system - Abstract
The brain-gut axis refers to the communication between the central nervous system and the gastrointestinal tract, with the gut microbiome playing a crucial role. While our understanding of the interaction between the gut microbiome and the host's physiology is still in its nascent stage, evidence suggests that the gut microbiota can indeed modulate host behavior. Understanding the specific mechanisms by which the gut microbiota community modulates the host's behavior remains the focus of present and future neuro-gastroenterology studies. This paper reviews several pieces of evidence from the literature on the impact of gut microbiota on host behavior across animal taxa. We explore the different pathways through which this modulation occurs, with the aim of deepening our understanding of the fascinating relationship between the gut microbiome and the central nervous system. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Pyroptosis in glioma: Current management and future application.
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Guo, Zeshang, Su, Zhenjin, Wei, Ying, Zhang, Xingmei, and Hong, Xinyu
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PYROPTOSIS , *GLIOMAS , *APOPTOSIS , *CYTOKINE release syndrome , *BLEPHAROPTOSIS , *CENTRAL nervous system - Abstract
Summary: Glioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5‐year survival rate. The efficacy of current treatment methods is limited by the presence of the blood–brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood–brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well‐established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma. [ABSTRACT FROM AUTHOR]
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- 2024
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46. From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).
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Fabbri, Laura, Di Federico, Alessandro, Astore, Martina, Marchiori, Virginia, Rejtano, Agnese, Seminerio, Renata, Gelsomino, Francesco, and De Giglio, Andrea
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NON-small-cell lung carcinoma , *CRIZOTINIB , *CLINICAL trials , *ANAPLASTIC large-cell lymphoma , *BLOOD-brain barrier , *BRAIN diseases - Abstract
Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Exploring the Central Mechanisms of Botulinum Toxin in Parkinson's Disease: A Systematic Review from Animal Models to Human Evidence.
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Cutrona, Carolina, Marchet, Francesco, Costanzo, Matteo, De Bartolo, Maria Ilenia, Leodori, Giorgio, Ferrazzano, Gina, Conte, Antonella, Fabbrini, Giovanni, Berardelli, Alfredo, and Belvisi, Daniele
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BOTULINUM A toxins , *BOTULINUM toxin , *PARKINSON'S disease , *ANIMAL models in research , *CENTRAL nervous system , *SENSORIMOTOR integration - Abstract
Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory–motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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48. Leptin and energy balance: exploring Leptin's role in the regulation of energy intake and energy expenditure.
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Tucker, Jessica A.L., Bornath, Derek P.D., McCarthy, Seth F., and Hazell, Tom J.
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LEPTIN receptors , *BRAIN-derived neurotrophic factor , *LEPTIN , *GHRELIN receptors , *PEPTIDES , *AMYLIN , *CENTRAL nervous system , *GHRELIN - Abstract
Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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49. Filtering property of myelinated internode can change neural information representability and might trigger a compensatory action during demyelination.
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Das, Sarbani and Maharatna, Koushik
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MYELIN proteins , *CENTRAL nervous system , *OLIGODENDROGLIA , *ACTION potentials , *DEMYELINATION , *MYELIN - Abstract
In this paper, for the first time, we showed that an Internode Segment (INS) of a myelinated axon acts as a lowpass filter, and its filter characteristics depend on the number of myelin turns. Consequently, we showed how the representability of a neural signal could be altered with myelin loss in pathological conditions involving demyelinating diseases. Contrary to the traditionally held viewpoint that myelin geometry of an INS is optimised for maximising Conduction Velocity (CV) of Action Potential (AP), our theory provides an alternative viewpoint that myelin geometry of an INS is optimised for maximizing representability of the stimuli a fibre is meant to carry. Subsequently, we show that this new viewpoint could explain hitherto unexplained experimentally observed phenomena such as, shortening of INS length during demyelination and remyelination, and non-uniform distribution of INS in the central nervous system fibres and associated changes in diameter of nodes of ranvier along an axon. Finally, our theory indicates that a compensatory action could take place during demyelination up to a certain number of loss of myelin turns to preserve the neural signal representability by simultaneous linear scaling of the length of an INS and the inner radius of the fibre. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
50. Signature methods for brain-computer interfaces.
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Xu, Xiaoqi, Lee, Darrick, Drougard, Nicolas, and Roy, Raphaëlle N.
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BRAIN-computer interfaces , *PERIPHERAL nervous system , *ITERATED integrals , *MOTOR imagery (Cognition) , *CENTRAL nervous system - Abstract
Brain-computer interfaces (BCIs) allow direct communication between one's central nervous system and a computer without any muscle movement hence by-passing the peripheral nervous system. They can restore disabled people's ability to interact with their environment, e.g. communication and wheelchair control. However, to this day their performance is still hindered by the non-stationarity of electroencephalography (EEG) signals, as well as their susceptibility to noise from the users' environment and from their own physiological activity. Moreover, a non-negligible amount of users struggle to use BCI systems based on motor imagery. In this paper, a new method based on the path signature is introduced to tackle this problem by using features which are different from the usual power-based ones. The path signature is a series of iterated integrals computed from a multidimensional path. It is invariant under translation and time reparametrization, which makes it a robust feature for multichannel EEG time series. The performance can be further boosted by combining the path signature with the gold standard Riemannian classifier in the BCI field exploiting the geometric structure of symmetric positive definite (SPD) matrices. The results obtained on publicly available datasets show that the signature method is more robust to inter-user variability than classical ones, especially on noisy and low-quality data. Hence, this study paves the way towards the use of mathematical tools that until now have been neglected, in order to tackle the EEG-based BCI variability issue. It also sheds light on the lead-lag relationship captured by path signature which seems relevant to assess the underlying neural mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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