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Cells Apr 2024Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate...
Subarachnoid hemorrhage (SAH) remains a major cause of cerebrovascular morbidity, eliciting severe headaches and vasospasms that have been shown to inversely correlate with vasodilator calcitonin gene-related peptide (CGRP) levels. Although dura mater trigeminal afferents are an important source of intracranial CGRP, little is known about the effects of SAH on these neurons in preclinical models. The present study evaluated changes in CGRP levels and expression in trigeminal primary afferents innervating the dura mater 72 h after experimentally induced SAH in adult rats. SAH, eliciting marked damage revealed by neurological examination, significantly reduced the density of CGRP-immunoreactive nerve fibers both in the dura mater and the trigeminal caudal nucleus in the medulla but did not affect the total dural nerve fiber density. SAH attenuated ex vivo dural CGRP release by ~40% and in the trigeminal ganglion, reduced both CGRP mRNA levels and the number of highly CGRP-immunoreactive cell bodies. In summary, we provide novel complementary evidence that SAH negatively affects the integrity of the CGRP-expressing rat trigeminal neurons. Reduced CGRP levels suggest likely impaired meningeal neurovascular functions contributing to SAH complications. Further studies are to be performed to reveal the importance of impaired CGRP synthesis and its consequences in central sensory processing.
Topics: Animals; Calcitonin Gene-Related Peptide; Dura Mater; Male; Rats; Subarachnoid Hemorrhage; Neurons; Rats, Sprague-Dawley; Trigeminal Ganglion; RNA, Messenger; Trigeminal Nerve
PubMed: 38667268
DOI: 10.3390/cells13080653 -
Animal Reproduction Science Jun 2024To assist in the conservation of collared peccary, it is important to strengthen semen processing protocols. The aim of this study was to compare the effects of... (Comparative Study)
Comparative Study
To assist in the conservation of collared peccary, it is important to strengthen semen processing protocols. The aim of this study was to compare the effects of different commercial extenders (BTS; NUTRIXcell+ and PRIMXcell Ultra) and TRIS + egg yolk on the functional and morphological aspects of collared peccary semen stored at 17 °C for 48 hours. Ten ejaculates obtained by electroejaculation were divided into 4 aliquots and diluted in the respective extenders, then stored in a biological incubator at 17 °C for 12, 24, 36, and 48 hours. The samples were evaluated for kinetic parameters, membrane functionality, membrane integrity, mitochondrial activity, morphology, and sperm-binding capacity. At the end of storage (48 h), promising results were found for motility parameters, with TRIS + egg yolk (71.0 ± 4.6%) being more efficient than NUTRIXcell+ (38.9 ± 10.9%) (P < 0.05) and similar to BTS (42.9 ± 11.9%) and PRIMXcell Ultra (46.8 ± 10.8%). The results for membrane integrity and mitochondrial activity were around ∼30-50%, with TRIS being the only extender to preserve both parameters (58.9 ± 5.3 and 59.2 ± 5.6%) for up to 48 hours, respectively (P < 0.05). Finally, the extenders could guarantee 60% membrane functionality and ∼ 60-70% normal sperm morphology, as well as similar binding capacity among the groups. In conclusion, TRIS + egg yolk is effective in preserving the sperm parameters of collared peccary semen at 17 °C for 48 hours, while PRIMXcell Ultra and BTS are viable alternatives for this purpose.
Topics: Animals; Semen Preservation; Male; Egg Yolk; Cryoprotective Agents; Semen Analysis; Artiodactyla; Tromethamine; Refrigeration; Spermatozoa; Semen
PubMed: 38663148
DOI: 10.1016/j.anireprosci.2024.107478 -
Toxicologic Pathology Apr 2024Nonclinical studies of test articles (TAs) in nonhuman primates are often designed to assess both biodistribution and toxicity. For this purpose, studies commonly use...
Nonclinical studies of test articles (TAs) in nonhuman primates are often designed to assess both biodistribution and toxicity. For this purpose, studies commonly use intravenous perfusion of ice-cold (2°C-8°C) saline to facilitate measurements of TA-associated nucleic acids and proteins, after which tissues undergo later fixation by immersion for histological processing and microscopic evaluation. Intriguingly, minimal apoptosis/single cell necrosis (A/SCN) of randomly distributed neural cells is evident in the cerebral cortex and less often the hippocampus in animals from all groups, including vehicle-treated controls. Affected cells exhibit end-stage features such as cytoplasmic hypereosinophilia, nuclear condensation or fragmentation, and shape distortions, so their lineage(s) generally cannot be defined; classical apoptotic bodies are exceedingly rare. In addition, A/SCN is not accompanied by glial reactions, leukocyte infiltration/inflammation, or other parenchymal changes. The severity is minimal in controls but may be slightly exacerbated (to mild) by TA that accumulate in neural cells. One plausible hypothesis explaining this A/SCN exacerbation is that cold shock (perhaps complicated by concurrent tissue acidity and hypoxia) drives still-viable but TA-stressed cells to launch a self-directed death program. Taken together, these observations indicate that A/SCN in brain processed by cold saline perfusion with delayed immersion fixation represents a procedural artifact and not a TA-related lesion.
PubMed: 38661106
DOI: 10.1177/01926233241247044 -
Frontiers in Medicine 2024The potential for secondary use of health data to improve healthcare is currently not fully exploited. Health data is largely kept in isolated data silos and key...
INTRODUCTION
The potential for secondary use of health data to improve healthcare is currently not fully exploited. Health data is largely kept in isolated data silos and key infrastructure to aggregate these silos into standardized bodies of knowledge is underdeveloped. We describe the development, implementation, and evaluation of a federated infrastructure to facilitate versatile secondary use of health data based on Health Data Space nodes.
MATERIALS AND METHODS
Our proposed nodes are self-contained units that digest data through an extract-transform-load framework that pseudonymizes and links data with privacy-preserving record linkage and harmonizes into a common data model (OMOP CDM). To support collaborative analyses a multi-level feature store is also implemented. A feasibility experiment was conducted to test the infrastructures potential for machine learning operations and deployment of other apps (e.g., visualization). Nodes can be operated in a network at different levels of sharing according to the level of trust within the network.
RESULTS
In a proof-of-concept study, a privacy-preserving registry for heart failure patients has been implemented as a real-world showcase for Health Data Space nodes at the highest trust level, linking multiple data sources including (a) electronical medical records from hospitals, (b) patient data from a telemonitoring system, and (c) data from Austria's national register of deaths. The registry is deployed at the tirol kliniken, a hospital carrier in the Austrian state of Tyrol, and currently includes 5,004 patients, with over 2.9 million measurements, over 574,000 observations, more than 63,000 clinical free text notes, and in total over 5.2 million data points. Data curation and harmonization processes are executed semi-automatically at each individual node according to data sharing policies to ensure data sovereignty, scalability, and privacy. As a feasibility test, a natural language processing model for classification of clinical notes was deployed and tested.
DISCUSSION
The presented Health Data Space node infrastructure has proven to be practicable in a real-world implementation in a live and productive registry for heart failure. The present work was inspired by the European Health Data Space initiative and its spirit to interconnect health data silos for versatile secondary use of health data.
PubMed: 38660421
DOI: 10.3389/fmed.2024.1301660 -
ELife Apr 2024Mutations in the human gene cause the neurodevelopmental PURA syndrome. In contrast to several other monogenetic disorders, almost all reported mutations in this...
Mutations in the human gene cause the neurodevelopmental PURA syndrome. In contrast to several other monogenetic disorders, almost all reported mutations in this nucleic acid-binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding, or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and nuclear magnetic resonance measurements. The observed unusually high dynamics and structural promiscuity of PURA indicated that this protein is particularly susceptible to mutations impairing its structural integrity. It offers an explanation why even conservative mutations across PURA result in the full penetrance of symptoms in patients with PURA syndrome.
Topics: Humans; Neurodevelopmental Disorders; Processing Bodies; Stress Granules; Crystallography, X-Ray; Dimerization; Protein Domains; Circular Dichroism; Recombinant Proteins; Protein Folding; Penetrance; Amino Acid Substitution; Point Mutation; HeLa Cells
PubMed: 38655849
DOI: 10.7554/eLife.93561 -
Journal of Cognitive Neuroscience Jun 2024Human faces and bodies represent various socially important signals. Although adults encounter numerous new people in daily life, they can recognize hundreds to...
Human faces and bodies represent various socially important signals. Although adults encounter numerous new people in daily life, they can recognize hundreds to thousands of different individuals. However, the neural mechanisms that differentiate one person from another person are unclear. This study aimed to clarify the temporal dynamics of the cognitive processes of face and body personal identification using face-sensitive ERP components (P1, N170, and N250). The present study performed three blocks (face-face, face-body, and body-body) of different ERP adaptation paradigms. Furthermore, in the above three blocks, ERP components were used to compare brain biomarkers under three conditions (same person, different person of the same sex, and different person of the opposite sex). The results showed that the P1 amplitude for the face-face block was significantly greater than that for the body-body block, that the N170 amplitude for a different person of the same sex condition was greater than that for the same person condition in the right hemisphere only, and that the N250 amplitude gradually increased as the degree of face and body sex-social categorization grew closer (i.e., same person condition > different person of the same sex condition > different person of the opposite sex condition). These results suggest that early processing of the face and body processes the face and body separately and that structural encoding and personal identification of the face and body process the face and body collaboratively.
Topics: Humans; Female; Male; Young Adult; Electroencephalography; Adult; Facial Recognition; Evoked Potentials; Time Perception; Social Perception; Brain
PubMed: 38652104
DOI: 10.1162/jocn_a_02167 -
European Journal of Radiology Jun 2024This review provides an overview of the current state of artificial intelligence (AI) technology for automated detection of breast cancer in digital mammography (DM) and... (Review)
Review
PURPOSE
This review provides an overview of the current state of artificial intelligence (AI) technology for automated detection of breast cancer in digital mammography (DM) and digital breast tomosynthesis (DBT). It aims to discuss the technology, available AI systems, and the challenges faced by AI in breast cancer screening.
METHODS
The review examines the development of AI technology in breast cancer detection, focusing on deep learning (DL) techniques and their differences from traditional computer-aided detection (CAD) systems. It discusses data pre-processing, learning paradigms, and the need for independent validation approaches.
RESULTS
DL-based AI systems have shown significant improvements in breast cancer detection. They have the potential to enhance screening outcomes, reduce false negatives and positives, and detect subtle abnormalities missed by human observers. However, challenges like the lack of standardised datasets, potential bias in training data, and regulatory approval hinder their widespread adoption.
CONCLUSIONS
AI technology has the potential to improve breast cancer screening by increasing accuracy and reducing radiologist workload. DL-based AI systems show promise in enhancing detection performance and eliminating variability among observers. Standardised guidelines and trustworthy AI practices are necessary to ensure fairness, traceability, and robustness. Further research and validation are needed to establish clinical trust in AI. Collaboration between researchers, clinicians, and regulatory bodies is crucial to address challenges and promote AI implementation in breast cancer screening.
Topics: Breast Neoplasms; Humans; Female; Artificial Intelligence; Mammography; Radiographic Image Interpretation, Computer-Assisted; Early Detection of Cancer
PubMed: 38640824
DOI: 10.1016/j.ejrad.2024.111457 -
Blood Advances Jun 2024von Willebrand factor (VWF) undergoes complex posttranslational modification within endothelial cells (ECs) before secretion. This includes significant N- and O-linked...
von Willebrand factor (VWF) undergoes complex posttranslational modification within endothelial cells (ECs) before secretion. This includes significant N- and O-linked glycosylation. Previous studies have demonstrated that changes in N-linked glycan structures significantly influence VWF biosynthesis. In contrast, although abnormalities in VWF O-linked glycans (OLGs) have been associated with enhanced VWF clearance, their effect on VWF biosynthesis remains poorly explored. Herein, we report a novel role for OLG determinants in regulating VWF biosynthesis and trafficking within ECs. We demonstrate that alterations in OLGs (notably reduced terminal sialylation) lead to activation of the A1 domain of VWF within EC. In the presence of altered OLG, VWF multimerization is reduced and Weibel-Palade body (WPB) formation significantly impaired. Consistently, the amount of VWF secreted from WPB after EC activation was significantly reduced in the context of O-glycosylation inhibition. Finally, altered OLG on VWF not only reduced the amount of VWF secreted after EC activation but also affected its hemostatic efficacy. Notably, VWF secreted after WPB exocytosis consisted predominantly of low molecular weight multimers, and the length of tethered VWF string formation on the surface of activated ECs was significantly reduced. In conclusion, our data therefore support the hypothesis that alterations in O-glycosylation pathways directly affect VWF trafficking within human EC. These findings are interesting given that previous studies have reported altered OLG on plasma VWF (notably increased T-antigen expression) in patients with von Willebrand disease.
Topics: von Willebrand Factor; Weibel-Palade Bodies; Humans; Polysaccharides; Glycosylation; Protein Transport; Endothelial Cells; Protein Processing, Post-Translational; Protein Multimerization
PubMed: 38640438
DOI: 10.1182/bloodadvances.2023012499 -
Journal of Agricultural and Food... May 2024Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature...
Cold-adapted proteases are capable of efficient protein hydrolysis at reduced temperatures, which offer significant potential applications in the area of low temperature food processing. In this paper, we attempted to characterize cold-adapted proteases from Antarctic krill. Antarctic krill possesses an extremely active autolytic enzyme system in their bodies, and the production of peptides and free amino acids accompanies the rapid breakdown of muscle proteins following the death. The crucial role of trypsin in this process is recognized. A cold-adapted trypsin named OUC-Pp-20 from Antarctic krill genome was cloned and expressed in . Recombinant trypsin is a monomeric protein of 26.8 ± 1.0 kDa with optimum reaction temperature at 25 °C. In addition, the catalytic specificity of OUC-Pp-20 was assessed by identifying its hydrolysis sites through LC-MS/MS. OUC-Pp-20 appeared to prefer Gln and Asn at the P1 position, which is an amino acid with an amide group in its side chain. Hydrolysis reactions on milk and shrimp meat revealed that it can effectively degrade allergenic components in milk and arginine kinase in shrimp meat. These findings update the current knowledge of cold-adapted trypsin and demonstrate the potential application of OUC-Pp-20 in low temperature food processing.
Topics: Animals; Euphausiacea; Hydrolysis; Cold Temperature; Trypsin; Substrate Specificity; Amino Acid Sequence; Tandem Mass Spectrometry; Enzyme Stability; Antarctic Regions
PubMed: 38628059
DOI: 10.1021/acs.jafc.4c00322 -
BMJ (Clinical Research Ed.) Apr 2024The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum...
The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) statement was published in 2015 to provide the minimum reporting recommendations for studies developing or evaluating the performance of a prediction model. Methodological advances in the field of prediction have since included the widespread use of artificial intelligence (AI) powered by machine learning methods to develop prediction models. An update to the TRIPOD statement is thus needed. TRIPOD+AI provides harmonised guidance for reporting prediction model studies, irrespective of whether regression modelling or machine learning methods have been used. The new checklist supersedes the TRIPOD 2015 checklist, which should no longer be used. This article describes the development of TRIPOD+AI and presents the expanded 27 item checklist with more detailed explanation of each reporting recommendation, and the TRIPOD+AI for Abstracts checklist. TRIPOD+AI aims to promote the complete, accurate, and transparent reporting of studies that develop a prediction model or evaluate its performance. Complete reporting will facilitate study appraisal, model evaluation, and model implementation.
Topics: Humans; Prognosis; Models, Statistical; Decision Support Techniques; Checklist
PubMed: 38626948
DOI: 10.1136/bmj-2023-078378