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The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.
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The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.
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Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , COVID-19 , SARS-CoV-2 , Animais , Humanos , Camundongos , Enzima de Conversão de Angiotensina 2/química , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Camundongos Transgênicos , Testes de Neutralização , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Spotting fake news is a critical problem nowadays. Social media are responsible for propagating fake news. Fake news propagated over digital platforms generates confusion as well as induce biased perspectives in people. Detection of misinformation over the digital platform is essential to mitigate its adverse impact. Many approaches have been implemented in recent years. Despite the productive work, fake news identification poses many challenges due to the lack of a comprehensive publicly available benchmark dataset. There is no large-scale dataset that consists of Indian news only. So, this paper presents IFND (Indian fake news dataset) dataset. The dataset consists of both text and images. The majority of the content in the dataset is about events from the year 2013 to the year 2021. Dataset content is scrapped using the Parsehub tool. To increase the size of the fake news in the dataset, an intelligent augmentation algorithm is used. An intelligent augmentation algorithm generates meaningful fake news statements. The latent Dirichlet allocation (LDA) technique is employed for topic modelling to assign the categories to news statements. Various machine learning and deep-learning classifiers are implemented on text and image modality to observe the proposed IFND dataset's performance. A multi-modal approach is also proposed, which considers both textual and visual features for fake news detection. The proposed IFND dataset achieved satisfactory results. This study affirms that the accessibility of such a huge dataset can actuate research in this laborious exploration issue and lead to better prediction models.
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Circumflex aorta is described as a retroesophageal aortic arch, with opposite-sided descending aorta forming a true vascular ring with ligamentum arteriosum. We report two cases of right-sided circumflex aorta with varied clinical presentation. Computed tomography diagnosed this vascular ring anomaly. The patients were managed with the aortic uncrossing procedure as a primary surgical strategy. Preoperative diagnosis and thorough planning were essential for the successful outcome. The patients did not have any residual symptoms of tracheal and esophageal compression on follow up.
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Phage display is a proven and widely used technology for selecting specific antibodies against desired targets. However, an immense amount of effort is required to identify and screen the desired positive clones from large and diverse combinatorial libraries. On the other hand, the selection of positive binding clones from synthetic and semi-synthetic libraries has an inherent bias toward clones with randomly produced amber stop codons, making it more difficult to identify desirable binding antibodies. To overcome the screening of desired clones with amber codons, we present a step-by-step approach for effective phage library screening to isolate useful antibodies. The procedure calls for creating a simple new vector system for soluble production of phage ELISA positive binding clones with one or more amber stop codons in their single-chain antibody fragment (scFv) gene sequences, which is otherwise difficult in standard screening. Graphical abstract.
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We used human semi-synthetic phage antibody gene libraries to select anti-SARS-CoV-2 RBD scFv antibody fragment and subsequent characterization of this novel tetravalent monoclonal antibody targeting conformational epitopes in the receptor binding domain of SARS-CoV-2. Binding studies suggest that II62 tetravalent antibody cross-reacts with RBD protein of SARS-CoV2 and its different variants of concerns. The epitope mapping data reveals that II62 tetravalent antibody targets an epitope that does not directly interferes with RBD: ACE2 interaction. Neutralization studies with live authentic SARS-CoV2 virus suggests that increase in valency of II62 mAb from monovalent to tetravalent doesn't perturbate virus interactions with the ACE2 expressing host cells in cytopathic effect-based (CPE) assay. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03272-6.
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Pineoblastoma is an extremely rare intracranial neoplasm, with increased risk of craniospinal metastasis. There is only one case reported in the literature who presented during pregnancy. Described here is a woman who presented at five months of gestation with recurrence of pineoblastoma, who had previously defaulted adjuvant therapy following surgical decompression. The challenges in the diagnosis and treatment of pineoblastoma and its effects on pregnancy are also discussed.
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Sentiment analysis research has been increasing tremendously in recent times due to the wide range of business and social applications. Sentiment analysis from unstructured natural language text has recently received considerable attention from the research community. In this paper, we propose a novel sentiment analysis model based on common-sense knowledge extracted from ConceptNet based ontology and context information. ConceptNet based ontology is used to determine the domain specific concepts which in turn produced the domain specific important features. Further, the polarities of the extracted concepts are determined using the contextual polarity lexicon which we developed by considering the context information of a word. Finally, semantic orientations of domain specific features of the review document are aggregated based on the importance of a feature with respect to the domain. The importance of the feature is determined by the depth of the feature in the ontology. Experimental results show the effectiveness of the proposed methods.
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Algoritmos , Inteligência Artificial , Semântica , Sensação/fisiologiaRESUMO
T-cell lymphoma (TCL) is a biologically diverse and uncommon group of lymphoid malignant diseases. Compared with its B-cell counterparts, TCL is notably more difficult to diagnose and manage owing to its rarity and biologic heterogeneity. Hepatosplenic TCL is an extremely rare subtype of TCL. A 37-year-old Indian male presented to his physician with swelling and pain in left hypochondrium. Clinical examination revealed pallor, icterus and massive splenomegaly. His blood examination revealed pancytopenia. His bone marrow biopsy was suggestive of lymphoma. Whole body F-18 flourodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan revealed diffuse increased metabolic activity in massively enlarged spleen, liver and bone marrow. There was no evidence of metabolically active lymphadenopathy anywhere in the body. Guided by the FDG PET/CT findings, a liver biopsy was advised. Liver histopathology revealed the presence of hepatosplenic TCL. A final diagnosis of hepatosplenic TCL with liver, spleen and bone marrow involvement was made. Even though rare, hepatosplenic TCL should be considered as a possible diagnosis in patients presenting with similar clinical picture and FDG PET/CT scan findings.