BackgroundPulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death.Methods13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts.ResultsThe combination of a unique pattern of early-onset lung fibrosis (at 12–15 years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components.ConclusionOur data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.
Background: Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). Severe COVID-19 is represented with acute respiratory distress syndrome (ARDS) that requires mechanical ventilation. Moreover, recent studies are reporting invasive fungal infection associated with severe COVID-19. It is unclear whether the prescription of immunotherapies such as corticosteroids, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself is risk factor for COVID-19-associated invasive pulmonary aspergillosis (CAPA). Hence, fungal infections present an additional uncertainty in managing COVID-19 patients and further compromise the outcome. Case study: Here we report a case of SARS-CoV-2 complicated by invasive pulmonary aspergillosis (IPA) in a patient with no traditional risk factors for IPA. Admitted to ICU due to ARDS on mechanical ventilation, the patient deteriorated clinically with unexplained increased of fraction of inspired oxygen (FiO2) requirement from 50% to 80%. Investigations showed borderline serum galactomannan, nonspecific radiological findings reported to be atypical for COVID-19, and the respiratory sample grew Aspergillus spp. Main diagnosis: COVID-19 related fungal infection. The patient was treated with antifungal therapy for four weeks. He improved clinically after one week of starting antimicrobial treatment. After a prolonged ICU stay (87 days) due to infection control precaution, he was discharged from the ICU and moved to a long-term facility for further management and support. Conclusions: This case highlights the diagnostic challenge in such cases. and the importance of early recognition of CAPA which can optimize therapy by administration of appropriate antifungal agents that may impact mortality.
An important means for disseminating information in social media platforms is by including URLs that point to external sources in user posts. In Twitter, we estimate that about 21% of the daily stream of English-language tweets contain URLs. We notice that NLP tools make little attempt at understanding the relationship between the content of the URL and the text surrounding it in a tweet. In this work, we study the structure of tweets with URLs relative to the content of the Web documents pointed to by the URLs. We identify several segments classes that may appear in a tweet with URLs, such as the title of a Web page and the user's original content. Our goals in this paper are: introduce, define, and analyze the segmentation problem of tweets with URLs, develop an effective algorithm to solve it, and show that our solution can benefit sentiment analysis on Twitter. We also show that the problem is an instance of the block edit distance problem, and thus an NP-hard problem.
Background: Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020 by the World Health Organization (WHO). Severe COVID-19 is represented with acute respiratory distress syndrome (ARDS) that requires mechanical ventilation. Moreover, recent studies are reporting invasive fungal infection associated with severe COVID-19. It is unclear whether the prescription of immunotherapies such as corticosteroids, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection itself is risk factor for COVID-19-associated invasive pulmonary aspergillosis (CAPA). Hence, fungal infections present an additional uncertainty in managing COVID-19 patients and further compromise the outcome. Case study: Here we report a case of SARS-CoV-2 complicated by invasive pulmonary aspergillosis (IPA) in a patient with no traditional risk factors for IPA. Admitted to ICU due to ARDS on mechanical ventilation, the patient deteriorated clinically with unexplained increased of fraction of inspired oxygen (FiO2) requirement from 50% to 80%. Investigations showed borderline serum galactomannan, nonspecific radiological findings reported to be atypical for COVID-19, and the respiratory sample grew Aspergillus spp. Main diagnosis: COVID-19 related fungal infection. The patient was treated with antifungal therapy for four weeks. He improved clinically after one week of starting antimicrobial treatment. After a prolonged ICU stay (87 days) due to infection control precaution, he was discharged from the ICU and moved to a long-term facility for further management and support. Conclusions: This case highlights the diagnostic challenge in such cases. and the importance of early recognition of CAPA which can optimize therapy by administration of appropriate antifungal agents that may impact mortality.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.